Gastric intestinal metaplasia (IM) is a precancerous lesion that is associated with an elevated risk of gastric carcinogenesis. Weiwei Decoction (WWD) is a promising traditional Chinese herbal formula widely employed in clinical for treating IM. Previous studies suggested the potential involvement of the olfactomedin 4 (OLFM4)/nucleotide-binding oligomerization domain 1 (NOD1)/caudal-type homeobox gene 2 (CDX2) signaling pathway in IM regulation.

To verify the regulation of the OLFM4/NOD1/CDX2 pathway in IM, specifically investigating WWD's effectiveness on IM through this pathway.

Immunohistochemistry for OLFM4, NOD1, and CDX2 was conducted on tissue microarray. GES-1 cells treated with chenodeoxycholic acid were utilized as IM cell models. OLFM4 short hairpin RNA (shRNA), NOD1 shRNA, and OLFM4 pcDNA were transfected to clarify the pathway regulatory relationships. Protein interactions were validated by co-immunoprecipitation. To explore WWD's pharmacological actions, IM rat models were induced using N-methyl-N'-nitro-N-nitrosoguanidine followed by WWD gavage. Gastric cells were treated with WWD-medicated serum. Cytokines and chemokines content were assessed by enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction.

The OLFM4/NOD1/CDX2 axis was a characteristic of IM. OLFM4 exhibited direct binding and subsequent down-regulation of NOD1, thereby sustaining the activation of CDX2 and promoting the progression of IM. WWD improved gastric mucosal histological lesions while suppressing intestinal markers KLF transcription factor 4, villin 1, and MUCIN 2 expression in IM rats. Regarding pharmacological actions, WWD suppressed OLFM4 and restored NOD1 expression, consequently reducing CDX2 at the mRNA and protein levels in IM rats. Parallel regulatory mechanisms were observed at the protein level in IM cells treated with WWD-medicated serum. Furthermore, WWD-medicated serum treatment strengthened OLFM4 and NOD1 interaction. In case of anti-inflammatory, WWD restrained interleukin (IL)-6, interferon-gamma, IL-17, macrophage chemoattractant protein-1, macrophage inflammatory protein 1 alpha content in IM rat serum. WWD-medicated serum inhibited tumor necrosis factor alpha, IL-6, IL-8 transcriptions in IM cells.

The OLFM4/NOD1/CDX2 pathway is involved in the regulation of IM. WWD exerts its therapeutic efficacy on IM through the pathway, additionally attenuating the inflammatory response.

Advanced rectal cancer with submesenteric lymph node metastasis is a common complication of advanced rectal cancer, which has an important impact on the treatment and prognosis of patients.

To investigate the clinical and pathological characteristics of inferior mesenteric artery (IMA) root lymph node metastases in patients with rectal cancer. The findings of this study provided us with fresh medical information that assisted us in determining the appropriate treatment for these patients.

Our study searched PubMed, Google Scholar, and other databases and searched the relevant studies and reports on the risk factors of IMA root lymph node metastasis of rectal cancer published in the self-built database until December 31, 2023. After data extraction, the Newcastle-Ottawa scale was used to evaluate the quality of the included literature, and RevMan5.3 software was used for meta-analysis and heterogeneity testing. The fixed effect modules without heterogeneity were selected to combine the effect size, and the random effect modules with heterogeneity were selected to combine the effect size. The cause of heterogeneity was found through sensitivity analysis, and the data of various risk factors were combined to obtain the final effect size, odds ratio (OR) value, and 95% confidence interval (CI). Publication bias was tested by drawing funnel plots.

A total of seven literature were included in this study. By combining the OR value of logistic multivariate regression and the 95%CI of various risk factors, we concluded that the risk factors for lymph node metastasis in the IMA region of rectal cancer were as follows: Preoperative carcinoembryonic antigen (CEA) > 5 ng/mL (OR = 0.32, 95%CI: 0.18-0.55, P < 0.05), tumor located above peritoneal reflexive (OR = 3.10, 95%CI: 1.78-5.42, P < 0.05), tumor size ≥ 5 cm (OR = 0.36, 95%CI: 0.22-0.57, P < 0.05), pathological type (mucinous adenocarcinoma/sig-ring cell carcinoma) (OR = 0.23, 95%CI: 0.13-0.41, P < 0.05), degree of tumor differentiation (low differentiation) (OR = 0.17, 95%CI: 0.10-0.31, P < 0.05), tumor stage (T3-4 stage) (OR = 0.11, 95%CI: 0.04-0.26, P < 0.05), gender and age were not risk factors for IMA root lymph node metastasis in rectal cancer (P > 0.05).

Preoperative CEA level, tumor location, tumor size, tumor pathologic type, tumor differentiation, and T stage were correlated with IMA root lymph node metastasis.

Hepatocellular carcinoma (HCC) is a malignant tumor that has a high incidence and mortality worldwide. Despite extensive studies, the detailed molecular mechanism of HCC development remains unclear. Studies have shown that the occurrence and development of HCC are closely related to abnormal gene expression. BCAR3 has been shown to be overexpressed in a variety of malignant tumors. However, the role of BCAR3 in HCC remains unclear.

To investigate the expression of BCAR3 and BCAR3-related competing endogenous RNAs (ceRNAs) in HCC and their clinical significance, in order to provide new ideas for the diagnosis and treatment of HCC.

The data of HCC were obtained from the Cancer Genome Atlas database and The Genotype Tissue Expression, including transcriptome data and clinical information. Multiple common databases, including UALCAN, Timer 2.0, cBioPortal, LinkedOmics, starBase, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, were used to analyse the expression of BCAR3, prognostic value, genetic alteration, co-expressed genes, differentially expressed genes, BCAR3 gene-related ceRNAs and functional enrichment analysis in HCC patients. Kaplan-Meier analysis, univariate and multivariate Cox regression analysis were used to analyze survival prognosis and the Spearman test was used to measure correlations between BCAR3 and immune functions. And R language package was used to analyze the correlation between BCAR3 and immune invasion of HCC.

Our study indicated that BCAR3 was differentially expressed in various tumor tissues. The over-expression of BCAR3 gene was an unfavorable prognostic indicator for HCC patients, and associated with unfavorable cytogenetic risk and gene mutations. Moreover, most immune cells were positively correlated with BCAR3 (P < 0.05). According to the results of functional enrichment analysis, BCAR3 was involved in the positive regulation of epidermal growth factor receptor signaling pathway and ERBB signaling pathway, and was related to DNA replication and GTPase regulator activity. Finally, our study found that based on RAB30-DT and miR-19b-3p pathways, targeting BCAR3 might promote the occurrence and development of HCC.

Collectively, this study indicated that the BCAR3 gene was involved in the occurrence and development of HCC, and it might be a new biomarker and therapeutic target for HCC, but the specific mechanism remains to be further verified.

Little is known about disparities in diagnosis and treatment among colorectal cancer (CRC) patients with and without disabilities.

To investigate the patterns of diagnosis, treatment, and survival for people with and without disabilities who had CRC.

We performed a retrospective analysis using the Korean National Health Insurance Service database, disability registration data, and Korean Central Cancer Registry data. The analysis included 21449 patients with disabilities who were diagnosed with CRC and 86492 control patients diagnosed with CRC.

The overall distribution of CRC stage was not affected by disability status. Subjects with disabilities were less likely than those without disabilities to undergo surgery [adjusted odds ratio (aOR): 0.85; 95% confidence interval (95%CI): 0.82-0.88], chemotherapy (aOR: 0.84; 95%CI: 0.81-0.87), or radiotherapy (aOR: 0.90; 95%CI: 0.84-0.95). The rate of no treatment was higher in patients with disabilities than in those without disabilities (aOR: 1.48; 95%CI: 1.41-1.55). The overall mortality rate was higher in patients with disabilities [adjusted hazard ratio (aHR): 1.24; 95%CI: 1.22-1.28], particularly severe disabilities (aHR: 1.57; 95%CI: 1.51-1.63), than in those without disabilities.

Patients with severe disabilities tended to have a late or unknown diagnosis. Patients with CRC and disabilities had lower rates of treatment with almost all modalities compared with those without disabilities. During the follow-up period, the mortality rate was higher in patients with disabilities than in those without disabilities. The diagnosis and treatment of CRC need improvement in patients with disabilities.

Gastric cancer (GC) is one of the most common malignancies worldwide. Glycolysis has been demonstrated to be pivotal for the carcinogenesis of GC.

To develop a glycolysis-based gene signature for prognostic evaluation in GC patients.

Differentially expressed genes correlated with glycolysis were identified in stomach adenocarcinoma data (STAD). A risk score was established through a univariate Cox and least absolute shrinkage and selection operator analysis. The model was evaluated using the area under the receiver operating characteristic curves. RNA-sequencing data from high- and low-glycolysis groups of STAD patients were analyzed using Cibersort algorithm and Spearman correlation to analyze the interaction of immune cell infiltration and glycolysis. Multiomics characteristics in different glycolysis status were also analyzed.

A five-gene signature comprising syndecan 2, versican, malic enzyme 1, pyruvate carboxylase and SRY-box transcription factor 9 was constructed. Patients were separated to high- or low-glycolysis groups according to risk scores. Overall survival of patients with high glycolysis was poorer. The sensitivity and specificity of the model in prediction of survival of GC patients were also observed by receiver operating characteristic curves. A nomogram including clinicopathological characteristics and the risk score also showed good prediction for 3- and 5-year overall survival. Gene set variation analysis showed that high-glycolysis patients were related to dysregulation of pancreas beta cells and estrogen late pathways, and low-glycolysis patients were related to Myc targets, oxidative phosphorylation, mechanistic target of rapamycin complex 1 signaling and G2M checkpoint pathways. Tumor-infiltrating immune cells and multiomics analysis suggested that the different glycolysis status was significantly correlated with multiple immune cell infiltration. The patients with high glycolysis had lower tumor mutational burden and neoantigen load, higher incidence of microsatellite instability and lower chemosensitivity. High glycolysis status was often found among patients with grade 2/3 cancer or poor prognosis.

The genetic characteristics revealed by glycolysis could predict the prognosis of GC. High glycolysis significantly affects GC phenotype, but the detailed mechanism needs to be further studied.

Lymph node metastasis (LNM) significantly impacts the treatment and prognosis of early gastric cancer (EGC). Consequently, the precise prediction of LNM risk in EGC patients is essential to guide the selection of appropriate surgical approaches in clinical settings.

To develop a novel nomogram risk model for predicting LNM in EGC patients, utilizing preoperative clinicopathological data.

Univariate and multivariate logistic regression analyses were performed to examine the correlation between clinicopathological factors and LNM in EGC patients. Additionally, univariate Kaplan-Meier and multivariate Cox regression analyses were used to assess the influence of clinical factors on EGC prognosis. A predictive model in the form of a nomogram was developed, and its discrimination ability and calibration were also assessed.

The incidence of LNM in the study cohort was 19.6%. Multivariate logistic regression identified tumor size, location, degree of differentiation, and pathological type as independent risk factors for LNM in EGC patients. Both tumor pathological type and LNM independently affected the prognosis of EGC. The model's performance was reflected by an area under the curve of 0.750 [95% confidence interval (CI): 0.701-0.789] for the training group and 0.763 (95%CI: 0.687-0.838) for the validation group.

A clinical prediction model was constructed (using tumor size, low differentiation, location in the middle-lower region, and signet ring cell carcinoma), with its score being a significant prognosis indicator.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the GI tract. They can occur throughout the GI tract, and the survival time of some patients can be improved by first-line targeted therapy with imatinib. However, there are some limitations with imatinib treatment. Immunotherapy for GIST has attracted much attention in recent years, and as one of the most abundant cells in the GIST microenvironment, M2 macrophages play an important role in disease progression. They have unique anti-inflammatory and pro-tumorigenic effects and are one target for immunotherapy. This review summarizes the connection between different factors and the programmed death receptor-1/programmed death ligand-1 pathway and M2 macrophages to reactivate or enhance anti-tumor immunity and improve imatinib efficacy, and to provide new ideas for GIST immunotherapy.

Subphrenic carcinoma has been identified as a significant risk factor for the thermal ablation of intrahepatic tumors, resulting in a high rate of residual tumor recurrence. Some studies have proposed that combination treatment with transarterial chemoembolization (TACE) followed by radiofrequency ablation is both feasible and safe for tumors in the subphrenic region. However, research specifically examining the therapeutic outcomes of combination therapy using TACE and microwave ablation (TACE-MWA) in subphrenic tumors is lacking.

To evaluate the efficacy and safety of TACE-MWA in patients with subphrenic hepatocellular carcinoma (HCC).

Between December 2017 and December 2021, 49 patients diagnosed with HCC ≤ 6 cm, who received TACE-MWA, were included in this retrospective cohort study. These patients were classified into subphrenic and non-subphrenic groups based on the distance between the diaphragm and the tumor margin. The rates of local tumor progression (LTP), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Complications were evaluated by using a grading system developed by the Society of Interventional Radiology.

After a median follow-up time of 38 mo, there were no significant differences in LTP between the subphrenic and non-subphrenic groups (27.3% and 22.2% at 5 years, respectively; P = 0.66), PFS (55.5% at 5 years in both groups; P = 0.91), and OS (85.0% and 90.9% in the subphrenic and non-subphrenic groups at 5 years; P = 0.57). However, a significantly higher rate of LTP was observed in subphrenic HCC > 3 cm compared to those ≤ 3 cm (P = 0.085). The dosage of iodized oil [hazard ratio (HR): 1.52; 95% confidence interval (CI): 1.11-2.08; P = 0.009] and multiple tumors (HR: 13.22; 95%CI: 1.62-107.51; P = 0.016) were independent prognostic factors for LTP. There were no significant differences in complication rates between the two groups (P = 0.549).

Combined TACE and MWA was practical and safe for managing subphrenic HCC. The efficacy and safety levels did not vary significantly when tumors outside the subphrenic region were treated.

Combination therapy has emerged as the focus of research for unresectable hepatocellular carcinoma (HCC). In recent years, several studies have explored the clinical efficacy and safety of the combination therapies of transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs).

To conduct an updated meta-analysis verifying the clinical benefits and adverse effects of the triple combination therapy for unresectable HCC.

All eligible cohort, non-randomized controlled, and randomized controlled trial studies from the PubMed, Web of Science, Embase, Cochrane Library, and MedLine databases up to March 20, 2024 were screened for the present meta-analysis. The study endpoints included complete response (CR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Stata 16/18 software was used for this meta-analysis, and a P value of <0.05 was considered statistically significant.

A total of 29 studies with 1754 patients were included. Among the patients who received the TACE therapy with TKIs and ICIs, the tumor response results revealed a pooled CR, ORR, and DCR of 14% [95%CI (0.11-0.18)], 61% [95%CI (0.55-0.66)], and 85% [95%CI (0.83-0.87)], respectively. In terms of the survival outcomes, the pooled median PFS and OS were 10.25 months [95%CI (9.31-11.18)] and 20.47 months [95%CI (18.98-21.97)], respectively. The pooled prevalence of all-grade AEs during the triple treatment was 90% [95%CI (0.84-0.94)] and that of grade ≥ 3 AEs was 32% [95%CI (0.24-0.42)].

The combination therapy of TACE, TKIs, and ICIs exhibits great clinical benefits for unresectable HCC in terms of tumor responses and survival outcomes without increasing the risk of severe AEs.

Metastatic breast cancer originating in the gastrointestinal tract is a rare occurrence. The limited number of cases has resulted in incomplete understanding of the disease, making it challenging to differentiate from primary breast cancer. While clinical history and immunohistochemical studies can aid in distinguishing between the two, the management principles and pathogenesis of gastrointestinal metastatic breast cancer remain controversial. The scarcity of data has hampered comprehensive knowledge. Our objective is to shed light on this rare disease through our case study.

Here, we report a case of breast metastasis from gastric cancer in a 43-year-old woman. This patient was admitted to our hospital with complaints of discomfort in the upper and middle abdomen persisting for two months, as well as black stools for over ten days. She underwent radical distal gastrectomy for gastric cancer, followed by postoperative chemotherapy. Three years later, the patient developed bilateral breast nodules. Imaging studies indicated a high probability of malignancy. She subsequently underwent a right modified radical mastectomy and excision of a left breast mass. Postoperative pathology revealed the right breast tumor was consistent with primary gastric cancer.

We present a case of breast metastasis from gastric cancer to contribute to the limited foundation of research into this rare disease.

Few studies have investigated the association between gestational age, birth weight, and esophageal cancer risk; however, causality remains debated. We aimed to establish causal links between genetic gestational age and birth weight traits and gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and esophageal adenocarcinoma (EA). Additionally, we explored if known risk factors mediate these links.

To analyze of the relationship between gestational age, birth weight and GERD, BE, and EA.

Genetic data on gestational age and birth weight (n = 84689 and 143677) from the Early Growth Genetics Consortium and outcomes for GERD (n = 467253), BE (n = 56429), and EA (n = 21271) from genome-wide association study served as instrumental variables. Mendelian randomization (MR) and mediation analyses were conducted using MR-Egger, weighted median, and inverse variance weighted methods. Robustness was ensured through heterogeneity, pleiotropy tests, and sensitivity analyses.

Birth weight was negatively correlated with GERD and BE risk [odds ratio (OR) = 0.78; 95% confidence interval (CI): 0.69-0.8] and (OR = 0.75; 95%CI: 0.60-0.9), respectively, with no significant association with EA. No causal link was found between gestational age and outcomes. Birth weight was positively correlated with five risk factors: Educational attainment (OR = 1.15; 95%CI: 1.01-1.31), body mass index (OR = 1.06; 95%CI: 1.02-1.1), height (OR = 1.12; 95%CI: 1.06-1.19), weight (OR = 1.13; 95%CI: 1.10-1.1), and alcoholic drinks per week (OR = 1.03; 95%CI: 1.00-1.06). Mediation analysis showed educational attainment and height mediated the birth weight-BE link by 13.99% and 5.46%.

Our study supports the protective role of genetically predicted birth weight against GERD, BE, and EA, independent of gestational age and partially mediated by educational attainment and height.

RNA binding motif 5 (RBM5) has emerged as crucial regulators in many cancers.

To explore more functional and mechanistic exploration of RBM5 since the lack of research on RBM5 in colorectal cancer (CRC) dictates that is essential.

Through Gene Expression Profiling Interactive Analysis, we analyzed RBM5 expression in colon adenocarcinoma and rectum adenocarcinoma tissues. For detecting the mRNA expression of RBM5, quantitative real time-polymerase chain reaction was performed. Protein expression levels of RBM5, hexokinase 2, lactate dehydrogenase A, phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), phosphorylated-protein kinase B (p-AKT), and AKT were determined via Western blot. Functionally, cell counting kit-8 and 5-ethynyl-2'-deoxyuridine (EDU) assay were performed to evaluate proliferation of CRC cells. Invasiveness and migration of CRC cells were evaluated through conducting transwell assays. Glucose consumption, lactate production and adenosine-triphosphate (ATP) production were measured through a glucose assay kit, a lactate assay kit and an ATP production assay kit, respectively. Besides, RNA immunoprecipitation assay, half-life RT-PCR and dual-luciferase reporter assay were applied to detect interaction between RBM5 and PTEN. To establish a xenotypic tumor mice, CRC cells were subcutaneously injected into the right flank of each mouse. Protein expression of RBM5, Ki67, and PTEN in tumor tissues was examined using immunohistochemistry staining. Haematoxylin and eosin staining was used to evaluate tumor liver metastasis in mice.

We discovered down-regulation of RBM5 expression in CRC tissues and cells. RBM5 overexpression repressed proliferation, migration and invasion of CRC cells. Meantime, RBM5 impaired glycolysis in CRC cells, presenting as decreased glucose consumption, decreased lactate production and decreased ATP production. Besides, RBM5 bound to PTEN mRNA to stabilize its expression. PTEN expression was positively regulated by RBM5 in CRC cells. The protein levels of PI3K and p-AKT were significantly decreased after RBM5 overexpression. The suppressive influences of RBM5 on glycolysis, proliferation and metastasis of CRC cells were partially counteracted by PTEN knockdown. RBM5 suppressed tumor growth and liver metastasis in vivo.

This investigation provided new evidence that RBM5 was involved in CRC by binding to PTEN, expanding the importance of RBM5 in the treatment of CRC.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. As liver cancer often presents no noticeable symptoms in its early stages, most patients are diagnosed at an advanced stage, complicating treatment. Therefore, the identification of new biomarkers is crucial for the early detection and treatment of HCC. Research on exportin-5 (XPO5) could offer new avenues for early diagnosis and improve treatment strategies.

To explore the role of XPO5 in HCC progression and its potential as a prognostic biomarker.

This study assessed XPO5 mRNA expression in HCC using The Cancer Genome Atlas, TIMER, and International Cancer Genome Consortium databases, correlating it with clinical profiles and disease progression. We performed in vitro experiments to examine the effect of XPO5 on liver cell growth. Gene Set Enrichment Analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology were used to elucidate the biological roles and signaling pathways. We also evaluated XPO5's impact on immune cell infiltration and validated its prognostic potential using machine learning.

XPO5 was significantly upregulated in HCC tissues, correlating with tumor grade, T-stage, and overall survival, indicating poor prognosis. Enrichment analyses linked high XPO5 expression with tumor immunity, particularly CD4 T cell memory activation and macrophage M0 infiltration. Drug sensitivity tests identified potential therapeutic agents such as MG-132, paclitaxel, and WH-4-023. Overexpression of XPO5 in HCC cells, compared to normal liver cells, was confirmed by western blotting and quantitative real-time polymerase chain reaction. The lentiviral transduction-mediated knockdown of XPO5 significantly reduced cell proliferation and metastasis. Among the various machine learning algorithms, the C5.0 decision tree algorithm achieved accuracy rates of 95.5% in the training set and 92.0% in the validation set.

Our analysis shows that XPO5 expression is a reliable prognostic indicator for patients with HCC and is significantly associated with immune cell infiltration.

Helicobacter pylori (H. pylori) colonizes the human gastric mucosa and is implicated in the development of gastric cancer (GC). The tumor microenvironment is characterized by hypoxia, where hypoxia-inducible factor-1α (HIF-1α) plays a key role as a transcription factor, but the mechanisms underlying H. pylori-induced HIF-1α expression and carcinogenesis remain unclear.

To explore the underlying mechanism of H. pylori-induced HIF-1α expression in promoting the malignant biological behavior of gastric epithelial cells (GES-1).

The study was conducted with human GES-1 cells in vitro. Relative protein levels of methyltransferase-like protein 14 (METTL14), HIF-1α, main proteins of the PI3K/AKT pathway, epithelial-mesenchymal transition (EMT) biomarkers, and invasion indicators were detected by Western blot. Relative mRNA levels of METTL14 and HIF-1α were detected by quantitative reverse transcription-polymerase chain reaction. mRNA stability was evaluated using actinomycin D, and the interaction between METTL14 and HIF-1α was confirmed by immunofluorescence staining. Cell proliferation and migration were evaluated by cell counting kit-8 assay and wound healing assay, respectively.

H. pylori promoted HIF-1α expression and activated the PI3K/AKT pathway. Notably, METTL14 was downregulated in H. pylori-infected gastric mucosal epithelial cells and positively regulated HIF-1α expression. Functional experiments showed that the overexpression of HIF-1α or knockdown of METTL14 enhanced the activity of the PI3K/AKT pathway, thereby driving a series of malignant transformation, such as EMT and cell proliferation, migration, and invasion. By contrast, the knockdown of HIF-1α or overexpression of METTL14 had an opposite effect.

H. pylori-induced underexpression of METTL14 promotes the translation of HIF-1α and accelerates tumor progression by activating the PI3K/AKT pathway. These results provide novel insights into the carcinogenesis of GC.

Colon adenocarcinoma (COAD) is a malignant tumor of the digestive system. The mechanisms underlying COAD development and progression are still largely unknown.

To identify the role of canopy FGF signaling regulator 3 (CNPY3) in the development and progression of COAD by using bioinformatic tools and functional experiments.

Bioinformatic data were downloaded from public databases. The associations of clinicopathological features, survival, and immune function with the expression of CNPY3 were analyzed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses and Gene Set Enrichment Analysis were used to explore the related pathways. Then, quantitative real-time PCR and immunohistochemistry were used for validation of CNPY3 expression in clinical samples and tumor cell lines. Cell lines with CNPY3 knockdown were constructed to further analyze gene functions. The functional experiments included proliferation, invasion, migration and apoptosis assays.

In both the TCGA cohort and the merged dataset, elevated CNPY3 expression was observed in tumor tissues. High CNPY3 expression correlated with adverse survival and compromised immune functions. Functional enrichment analysis suggested that the pro-oncogenic properties of CNPY3 might be linked to the PI3K-AKT signaling pathway. CNPY3 expression was validated at both the RNA and protein levels. Functional assays indicated that cell proliferation, invasion, and migration were inhibited and cell apoptosis was promoted after CNPY3 knockdown. Additionally, Western blot results revealed the downregulation of key proteins in the PI3K/AKT pathway following CNPY3 knockdown. PI3K/AKT pathway activator reversed the decrease in proliferation, invasion, and migration and the increase in apoptosis. Notably, CNPY3 knockdown still affected the cells when the pathway was inhibited.

This study showed that CNPY3 is upregulated in COAD and might regulate COAD development and progression by the PI3K/AKT pathway. Thus, CNPY3 might be a promising therapeutic target.

The combination of transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) has shown broad prospects in prolonging the survival of patients with hepatocellular carcinoma (HCC). TACE and TKIs can affect the immune microenvironment in patients with HCC.

To determine the overall effects and differences between TACE and different TKIs combinations on the immune microenvironment.

Data and immune cell profile test results from 213 HCC patients treated with TACE combined with apatinib, lenvatinib, sorafenib, or donafenib before and after 3 wk of treatment were collected. Monocytes were co-cultured with LM3 liver cancer cells, and their ability to inhibit cancer cell growth was analyzed using the MTT method and a nude mouse subcutaneous tumorigenesis experiment. Simulated combined therapy was done using an in situ liver cancer C57BL/6 male mouse model, and the immune response of tumor tissues was analyzed using immunohistochemistry.

Compared to before combination therapy, the proportion of programmed cell death protein 1 (PD-1)+ mononuclear cells and the number of CD4+ T cells decreased in the TACE + apatinib group, while the number of absolute count of CD4+ and CD8+ T cells increased in the TACE + lenvatinib group. Furthermore, the number of regulatory cells decreased in the TACE + donafenib group, whereas the number of CD8+ T and natural killer cells increased. Additionally, monocytes in the TACE combined with donafenib or lenvatinib groups had a stronger ability to inhibit cancer cell growth than those in the other groups. Combining TACE with donafenib or lenvatinib increased CD8+ T cell infiltration into the tumor tissue. In addition, the proportion of PD-1+ in CD8+ cells, absolute CD8+ T lymphocyte count, and regulatory T cells proportion were independent prognostic factors affecting the survival time of patients with HCC.

TACE, in combination with different TKIs, produces different immune responses. Specifically, TACE combined with donafenib or lenvatinib may induce strong anti-tumor immune responses.

Aldehyde (ALDH2) dysfunction has been verified to contribute to human cancers.

To investigate the molecular mechanism and biological function of ALDH2 in colorectal cancer (CRC) progression.

Human CRC cells with high expression of ALDH2 were screened. After shRNA ALDH2 (sh-ALDH2) transfection, phenotypes [proliferation, apoptosis, acetaldehyde (ACE) accumulation, DNA damage] of CRC cells were verified using cell counting kit-8, flow cytometry, ACE assay, and comet assays. Western blotting was used for evaluation of the apoptosis proteins (Bax and Bcl-2) and JNK/p38 MAPK pathway-associated proteins. We subjected CVT-10216 (a selective ALDH2 inhibitor) to nude mice for establishment of SK-CO-1 mouse xenograft model and observed the occurrence of CRC.

The inhibition of ALDH2 could promote the malignant structures of CRC cells, including apoptosis, ACE level, and DNA damage, and cell proliferation was decreased in the sh-ALDH2 group, whereas ALDH2 agonist Alda-1 reversed features. ALDH2 repression can cause ACE accumulation, whereas ACE enhanced CRC cell features related to increased DNA damage. Additionally, ALDH2 repression led to JNK/P38 MAPK activation, and apoptosis, ACE accumulation, and DNA damage were inhibited after p38 MAPK inhibitor SB203580 and JNK inhibitor SP600125 addition. ACE accumulation and raised DNA damage were recognized in CVT-10216 treated-mouse tumor tissues in vivo.

The repression of ALDH2 led to ACE accumulation, inducing cell apoptosis and DNA damage by the JNK/p38 MAPK signaling pathway activation in CRC.

The incidence of multiple primary carcinomas (MPC) varies greatly, ranging from 0.73% to 11.70% in foreign countries, with duo-duplex carcinoma being the most common, trio-duplex carcinoma and above being rare, and simultaneous multigenic carcinoma being even rarer, accounting for 18.4% to 25.3% of the incidence of MPC. However, there is no report regarding patients presenting with simultaneous dual-origin carcinoma of the liver and colon and heterochronous pancreatic cancer.

We report a special case of multifocal carcinoma, in which one patient had a medical condition of primary liver and colon cancer and pancreatic cystadenocarcinoma 2 years after surgery. Through aggressive advanced fluorescent laparoscopic techniques, standardized immunotherapy, targeting, and chemotherapy, a better prognosis and a desirable survival period were achieved for the patient.

There is a need to clarify the nature of MPC through advanced surgical means to ensure better diagnosis and treatment.

Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in patient management due to a dismal prognosis, increasing incidence, and limited treatment options. In this regard, precision medicine, which personalizes treatments based on tumour molecular characteristics, has gained great interest. However, its widespread implementation is not fully endorsed in current recommendations. This review explores key molecular alterations in PDAC, while emphasizing differences between KRAS-mutated and KRAS-wild-type tumours. It assesses the practical application of precision medicine in clinical settings and outlines potential future directions with respect to PDAC. Actionable molecular targets are examined with the aim of enhancing our understanding of PDAC molecular biology. Insights from this analysis may contribute to a more refined and personalized approach to pancreatic cancer treatment, ultimately improving patient outcomes.

The publication by Qu et al provided a comprehensive discussion about the epidemiology, etiology, histopathology, early detection, and endoscopic treatment of esophageal carcinoma (EC) and summarized the progress in the advanced technologies for screening and endoscopic resection for EC. In this editorial, we will provide deeper insight into the challenges that hinder practical application of these advanced technologies along with the role of these technologies in upper endoscopy quality. More efforts need to be made to overcome the challenges and add the value of these technologies in upper endoscopy quality. Clinical outcomes of management strategies after noncurative endoscopic dissection for early EC patients need further investigation. The experiences with noncurative endoscopic resection of other organs may have certain implications for noncurative resection of early EC.

Esophageal carcinoma (EC) is one of the most prevalent cancers in human populations worldwide. Baitouweng decoction is one of the most important Chinese medicine formulas, with the potential to treat cancer.

To investigate the role and mechanism of Baitouweng decoction on EC cells.

Differentially expressed genes (DEGs) in EC tissues and normal tissues were screened by the cDNA microarray technique and by bioinformatics methods. The target genes of microRNAs were predicted based on the TargetScan database and verified by dual luciferase gene reporter assay. We used Baitouweng decoction to intervene EC cells, and detected the activity of EC9706 and KYSE150 cells by the MTT method. Cell cycle and apoptosis were measured by flow cytometry. The expression of BUB1 mRNA and miR-495-3p was measured by qRT-PCR. The protein levels of BUB1, STAT3, p-STAT3, CCNB1, CDK1, Bax, Caspase3, and Caspase9 were measured by Western blot analysis. The migration and invasion abilities of the cells were measured by wound-healing assay and Transwell invasion assay, respectively.

DEGs identified are involved in biological processes, signaling pathways, and network construction, which are mainly related to mitosis. BUB1 was the key hub gene, and it is also a target gene of miR-495-3p. Baitouweng decoction could upregulate miR-495-3p and inhibit BUB1 expression. In vitro experiments showed that Baitouweng decoction significantly inhibited the migration and invasion of EC cells and induced apoptosis and G2/M phase arrest. After treatment with Baitouweng decoction, the expression of Bax, Caspase 3, and Caspase 9 in EC cells increased significantly, while the expression of BUB1, CCNB1, and CDK1 decreased significantly. Moreover, the STAT3 signaling pathway may play an important role in this process.

Baitouweng decoction has a significant inhibitory effect on EC cell growth. BUB1 is a potential therapeutic target for EC. Further analysis showed that Baitouweng decoction may inhibit the growth of EC cells by upregulating miR-495-3p targeting the BUB1-mediated STAT3 signal pathway.

The immune microenvironment (IME) in hepatocellular carcinoma (HCC) plays a pivotal role in determining patient outcomes and responses to treatment. This area is witnessing rapid growth in research interest. However, there is a lack of comprehensive bibliometric analyses that dissect trends and potential focal points in this field.

To explore the evolution of research on the IME in HCC from January 1, 2004, to December 31, 2023, using bibliometric methodologies.

English articles and reviews concerning the IME of HCC were retrieved from the Web of Science Core Collection with a search date of December 31, 2023. The R package Bibliometrix was employed to compute basic bibliometric characteristics, illustrate collaborations among countries and authors, and create a three-field diagram illustrating the connections between authors, affiliations, and keywords. Analyses of country and institutional co-authorship, as well as keyword co-occurrence, were conducted using VOSviewer. Additionally, CiteSpace was utilized for the cite burst analysis of keywords and cited literature.

The study encompassed 3125 documents in the research areas related to HCC of IME, revealing a substantial and continuous increase in the annual publication trend over time. China and Fudan University emerged as leading contributors, with 2103 and 165 publications, respectively. Frontiers in immunology was the most prolific journal in this domain. Among the top ten researchers in the field, eight are based in China. Key research terms identified include tumour microenvironment, expression, immunotherapy, and prognosis.

The relationship between HCC and IME is receiving increasing attention, and related research is in a highly developed stage. Key focus areas, including IME and immune checkpoint inhibitors, immunotherapy are poised to be central to future research endeavors, offering promising pathways for further exploration.

In this editorial we comment on the article published in a recent issue of the World Journal of Gastrointestinal Oncology. Characterized by high mortality rates and geographical variations in its incidence, esophageal cancer poses a major global health challenge. This editorial article synthesizes insights from the review of esophageal cancer conducted by Qu et al, which highlights the importance of tailored screening and treatment strategies. Key themes include the effect of regional disparities on screening protocols, advancements in early detection methodologies, and therapeutic management disparities between different regions. By embracing personalized approaches grounded in regional nuances and technological innovation, the article advocates for comprehensive and collaborative efforts to improve patient outcomes in esophageal cancer care.

BRAF mutation has been recognized as a negative prognostic marker for metastatic colorectal cancer (mCRC), but these data are from common BRAF V600E-mutated mCRC. Combination therapy of BRAF inhibitor and anti-epidermal growth factor receptor (EGFR) antibody has been approved for BRAF V600E-mutated mCRC. However, BRAF non-V600 mutations are rare mutations, and their clinical behavior is not understood. Moreover, the BRAF K601E mutation is extremely rare in mCRC, and there have been no reports on its specific treatment.

Herein, we report the case of a 59-year-old female with super aggressive mCRC with multiple metastases, which extended to whole body including mediastinal to abdominal lymph nodes, bones, pleura, and peritoneum. The companion diagnostics of tumor tissues showed RAS/BRAF wild-type without microsatellite instability. She received chemotherapy with mFOLFOX6 (oxaliplatin plus infusional 5-fluorouracil [5-FU] and leucovorin) plus panitumumab, following FOLFIRI (irinotecan plus infusional 5-FU and leucovorin) plus ramucirumab. For the next regimen selection, a comprehensive genomic profiling panel was performed and revealed a BRAF K601E mutation, which was not covered in the initial companion diagnostics. After disease progression, a combination of encorafenib, binimetinib, and cetuximab was selected as third-line chemotherapy. The serum levels of tumor markers were immediately decreased accompanied by improvements in pleural effusion and ascites. However, the disease progressed again, and best supportive care was done instead.

This case offers novel insights into the clinical behaviors of BRAF non-V600E-mCRC, potentially advancing personalized therapy for rare and aggressive cases.

Angiogenesis plays an important role in colon cancer (CC) progression.

To investigate the tumor microenvironment (TME) and intratumor microbes of angiogenesis subtypes (AGSs) and explore potential targets for antiangiogenic therapy in CC.

The data were obtained from The Cancer Genome Atlas database and Gene Expression Omnibus database. K-means clustering was used to construct the AGSs. The prognostic model was constructed based on the differential genes between two subtypes. Single-cell analysis was used to analyze the expression level of SLC2A3 on different cells in CC, which was validated by immunofluorescence. Its biological functions were further explored in HUVECs.

CC samples were grouped into two AGSs (AGS-A and AGS-B) groups and patients in the AGS-B group had poor prognosis. Further analysis revealed that the AGS-B group had high infiltration of TME immune cells, but also exhibited high immune escape. The intratumor microbes were also different between the two subtypes. A convenient 6-gene angiogenesis-related signature (ARS), was established to identify AGSs and predict the prognosis in CC patients. SLC2A3 was selected as the representative gene of ARS, which was higher expressed in endothelial cells and promoted the migration of HUVECs.

Our study identified two AGSs with distinct prognoses, TME, and intratumor microbial compositions, which could provide potential explanations for the impact on the prognosis of CC. The reliable ARS model was further constructed, which could guide the personalized treatment. The SLC2A3 might be a potential target for antiangiogenic therapy.