The role of SWI/SNF complexes in digestive system neoplasms.

Chromatin remodeling is a critical step in the DNA damage response, and the ATP-dependent chromatin remodelers are a group of epigenetic regulators that alter nucleosome assembly and regulate transcription factor accessibility to DNA, preventing genomic instability and tumorigenesis caused by DNA damage. The SWI/SNF chromatin remodeling complex is one of them, and mutations in the gene encoding the SWI/SNF subunit are frequently found in digestive tumors. We review the most recent literature on the role of SWI/SNF complexes in digestive tumorigenesis, with different SWI/SNF subunits playing different roles. They regulate the biological behavior of tumor cells, participate in multiple signaling pathways, interact with multiple genes, and have some correlation with the prognosis of patients. Their carcinogenic properties may help discover new therapeutic targets. Understanding the mutations and defects of SWI/SNF complexes, as well as the underlying functional mechanisms, may lead to new strategies for treating the digestive system by targeting relevant genes or modulating the tumor microenvironment.

Identification roles of NFE2L3 in digestive system cancers.

BACKGROUND: Morbidity and mortality rates of Digestive System Cancers (DSC) continue to pose human lives and health. Nuclear factor erythroid 2-like protein 3 (NFE2L3) is aberrantly expressed in DSC. This study aimed to explore the clinical value and underlying mechanisms of NFE2L3 as a novel biomarker in DSC. METHODS: We utilized data from databases and clinical gastric cancer specimens to validate the aberrant expression level of NFE2L3 and further assessed the clinical value of NFE2L3. To investigate the potential molecular mechanism of NFE2L3, we analyzed the correlation of NFE2L3 with immune molecular mechanisms, constructed PPI network, performed GO analysis and KEGG analysis, and finally explored the biological function of NFE2L3 in gastric cancer cells. RESULTS: NFE2L3 expression is up-regulated in DSC and has both prognostic and diagnostic value. NFE2L3 correlates with various immune mechanisms, PPI network suggests proteins interacting with NFE2L3, GSEA analysis suggests potential molecular mechanisms for NFE2L3 to play a role in cancer promotion, and in vitro cellular experiments also confirmed the effect of NFE2L3 on the biological function of gastric cancer cells. CONCLUSION: Our study confirms the aberrant expression and molecular mechanisms of NFE2L3 in DSC, indicating that NFE2L3 could serve as a novel biomarker for diagnosis and prognosis of DSC.

Emerging function of main RNA methylation modifications in the immune microenvironment of digestive system tumors.

Digestive system tumors have been reported in more than 25% of all cancer cases worldwide, bringing a huge burden on the healthcare system. RNA methylation modification-an important post-transcriptional modification-has become an active research area in gene regulation. It is a dynamic and reversible process involving several enzymes, such as methyltransferases, demethylases, and methylation reader proteins. This review provides insights into the role of three major methylation modifications, namely m6A, m5C, and m1A, in the development of digestive system tumors, specifically in the development of tumor immune microenvironment (TIME) of these malignancies. Abnormal methylation modification affects immunosuppression and antitumor immune response by regulating the recruitment of immune cells and the release of immune factors. Understanding the mechanisms by which RNA methylation regulates digestive system tumors will be helpful in exploring new therapeutic targets.

Intratumoral microorganisms in tumors of the digestive system.

Tumors of the digestive system pose a significant threat to human health and longevity. These tumors are associated with high morbidity and mortality rates, leading to a heavy economic burden on healthcare systems. Several intratumoral microorganisms are present in digestive system tumors, and their sources and abundance display significant heterogeneity depending on the specific tumor subtype. These microbes have a complex and precise function in the neoplasm. They can facilitate tumor growth through various mechanisms, such as inducing DNA damage, influencing the antitumor immune response, and promoting the degradation of chemotherapy drugs. Therefore, these microorganisms can be targeted to inhibit tumor progression for improving overall patient prognosis. This review focuses on the current research progress on microorganisms present in the digestive system tumors and how they influence the initiation, progression, and prognosis of tumors. Furthermore, the primary sources and constituents of tumor microbiome are delineated. Finally, we summarize the application potential of intratumoral microbes in the diagnosis, treatment, and prognosis prediction of digestive system tumors. Video Abstract.

Analysis of Correlation between Rab1A Expression and its Prognosis in Cancers: a Meta-Analysis.

BACKGROUND: Rab1A not only regulates eukaryotic secretion, autophagy and intracellular traffic, but also extensively participates in the development of cancer. Thus, we collected data to investigate the clinical value of Rab1A in cancers. METHODS: English web database was searched for appropriate studies. The role of Rab1A in cancer patients was evaluated by combining hazard ratios and odds ratios. RESULTS: There were 15 studies in 14 articles, including 1,791 cancer patients. The results showed that upregulated Rab1A led to poor prognosis in cancer patients (pooled HR = 2.545, 95% CI = 1.924 - 3.367, p < 0.001). Notably, a high level of Rab1A was associated with a poorer prognosis than patients with a low level of Rab1A in digestive system cancer (pooled HR = 2.484, 95% CI = 1.796 - 3.437, p < 0.001). In order to explore the possible carcinogenic mechanism, we further analyzed and confirmed that high expression of Rab1A was associated with worse histologic grade, deeper tumor invasion, higher TNM stage, positive LN metastasis, positive neural invasion, positive vascular invasion, and larger tumor size (p < 0.05). CONCLUSIONS: Rab1A overexpression was associated with poor prognosis and adverse clinicopathological parameters in cancer patients and had the potential to be a target for future cancer therapy.

The Diagnostic Value of Circulating miR-29 Family for Digestive System Malignancies: A Meta-Analysis.

OBJECTIVE: To evaluate the diagnostic value of circulating microRNA-29 (miR-29) in digestive system malignant neoplasms by meta-analysis. METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science to collect studies, published through September 2022, on the diagnostic value of miR-29 in digestive system tumors. RESULTS: We included 7 studies in this meta-analysis, including colorectal cancer, esophageal squamous cell carcinomas, and cholangiocarcinoma. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.64 (95% CI, 0.53-0.74), 0.83 (0.60-0.94), 3.75 (1.42-9.91), 0.44 (0.31-0.61), and 8.63 (2.54-29.26), respectively. The area under the summary receiver operating characteristic curve was 0.75. The sensitivity of miR-29 derived from serum was higher than that of miR-29 derived from plasma for malignant digestive system tumors (0.71 vs 0.54; P = .04). CONCLUSION: This meta-analysis suggests that the circulating miR-29 family has good diagnostic performance for digestive system malignant tumors, with moderate sensitivity and good specificity.

The Functional Mechanisms of Toll-Like Receptor 3 and Its Implications in Digestive System Tumors.

Toll-like receptor 3 (TLR3) is a prominent member of the Toll-like receptor (TLR) family and has the ability to recognize and bind intracellular double-stranded RNA (dsRNA). Once triggered by a viral infection or other pathological condition, TLR3 activates immune cells and induces the production of interferons and other immune response molecules. Additionally, TLR3 is considered an important immune modulator, as it can regulate cell apoptosis and promote anticancer immunity. The investigation and application of TLR3 agonists in digestive system tumors have attracted widespread attention and are regarded as a promising cancer treatment strategy with potential clinical applications. TLR3 expression levels are generally elevated in most digestive system tumors, and higher TLR3 expression is associated with a better prognosis. Therefore, TLR3 has emerged as a novel therapeutic target for digestive system tumors. It has been used in combination with chemotherapy, radiotherapy, and targeted therapy and demonstrated excellent efficacy and tolerability. This has provided new ideas and hopes for the treatment of digestive system tumors. This review discusses the mechanisms of TLR3 and its frontier research in digestive system tumors.

The association of serum choline concentrations with the risk of cancers: a community-based nested case-control study.

Few studies have been designed to investigate the effect of serum choline on the risk of incident cancer. This study aims to explore the association between serum choline and the risk of new-onset cancer. We conducted a case-control study, including 199 patients with incident cancer and 199 matched controls during a median of 3.9 years of follow-up, nested within the China Stroke Primary Prevention Trial. Cubic spline regression (RCS) and conditional logistic regression analysis was used to assess the association of serum choline and incident cancer risk. We observed a positive dose-response association between serum choline levels and the risk of overall (p for overall = 0.046) and digestive system cancer (p for overall = 0.039). Compared with patients with the lowest choline levels (Q1 group), patients in the highest levels of choline (Q4) had a 3.69-fold and 6.01-fold increased risk of overall (OR = 3.69, 95% CI 1.17-11.63) and digestive system cancer (OR = 6.01, 95% CI 1.14-31.67). Elevated choline levels (per SD, 11.49 µg/mL) were associated with a higher risk of overall cancer among participants who were older, male, and smokers in the subgroup analyses. We found a positive association between elevated levels of serum choline with increased risk of incident cancer. Our findings have critical clinical implications for cancer prevention and diagnosis.Trial registration CSPPT, NCT00794885. Registered: November 20, 2008. https://www.clinicaltrials.gov/ct2/show/study/NCT00794885 https://www.clinicaltrials.gov/ct2/show/study/NCT00794885.

The Potential of Glycyrrhiza from "Medicine Food Homology" in the Fight against Digestive System Tumors.

Glycyrrhiza has a long history of applications and a wide range of pharmacological effects. It is known as the "king of all herbs". Glycyrrhiza is effective in clearing heat, detoxifying, relieving cough, and tonifying qi and has good bioactivity in multiple inflammatory, immune, and tumor diseases. This review aims to summarize the origin, distribution, and anti-digestive system tumor mechanism of glycyrrhiza and its homologous applications in medicine and food. The active compounds include triterpenoids, flavonoids, and coumarins, which are widely used in clinical treatments, disease prevention, and daily foods because of their "enhancement of efficacy" and "reduction of toxicity" against digestive system tumors. This paper reviews the use of glycyrrhiza in digestive system tumors and provides an outlook on future research and clinical applications.

Prognostic value of tertiary lymphoid structures (TLS) in digestive system cancers: a systematic review and meta-analysis.

BACKGROUND: Existing literature suggests that tertiary lymphatic structure (TLS) is associated with the progression of cancer. However, the prognostic role of TLS in digestive system cancers remains controversial. This meta-analysis aims to synthesize currently available evidence in the association between TLS and the survival of digestive system cancers. METHODS: We systematically searched three digital databases (PubMed, Embase, Web of Science) for articles published from database inception to December 23, 2022. Study selection criteria are based on PECO framework: P (population: patients with digestive system cancers), E (exposure: presence of TLS), C (comparator: absence of TLS), O (outcome: overall survival, OS; recurrence-free survival, RFS; disease-free survival, DFS). The Quality in Prognostic Studies (QUIPS) tool was used to assess risk of bias for included studies. The study protocol was registered with PROSPERO (CRD42023416307). RESULTS: A total of 25 studies with 6910 patients were included into the final meta-analysis. Random-effects models revealed that the absence of TLS was associated with compromised OS, RFS, and DFS of digestive system cancers, with pooled hazard ratios (HRs) of 1.74 (95% CI: 1.50-2.03), 1.96 (95% CI: 1.58-2.44), and 1.81 (95% CI: 1.49-2.19), respectively. Subgroup analyses disclosed a stronger TLS-survival association for pancreatic cancer, compared with other digestive system cancers. CONCLUSION: TLS may be of prognostic significance for digestive system cancers. More original studies are needed to further corroborate this finding.

Does proton pump inhibitors use increase risk of digestive tumors?: A 2-sample Mendelian randomization study.

The objective of this study was to explore the causal relationship between the use of proton pump inhibitors (PPIs) and 16 types of digestive system tumors. We utilized a 2-sample Mendelian randomization (MR) approach to investigate this relationship. We obtained exposure and outcome data from the UK Biobank and the Finland Biobank, respectively. The genetic data used in the analysis were derived from genome-wide association studies (GWAS) studies conducted on European populations. We screened single nucleotide polymorphisms significantly associated with the use of omeprazole, a commonly used PPIs, as instrumental variables. We then performed MR analyses using the inverse variance weighting (IVW) method, MR-Egger regression, and the weighted median method to evaluate the causal effect of omeprazole use on the 16 types of digestive system tumors. Our MR analysis revealed a significant causal relationship between the use of omeprazole and pancreatic malignancies, but not with any other types of digestive system tumors. The IVW analysis showed an odds ratio of 4.33E-05 (95%CI: [4.87E-09, 0.38], P = .03) and the MR-Egger analysis showed an odds ratio of 5.81E-11 (95%CI: [2.82E-20, 0.12], P = .04). We found no significant heterogeneity or pleiotropy, and sensitivity analysis confirmed the robustness of our results. Furthermore, statistical power calculations suggested that our findings were reliable. Conclusion The use of PPIs is a protective factor for pancreatic malignancies, but no causal relationship has been found with other digestive system tumors.

The short- and long-term readmission of four major categories of digestive system cancers: does obesity or metabolic disorder matter?

Purpose: Patients with digestive system cancers (DSCs) are at a high risk for hospitalizations; however, the risk factors for readmission remain unknown. Here, we established a retrospective cohort study to assess the association between metabolic obesity phenotypes and readmission risks of DSC. Experimental design: A total of 142,753 and 74,566 patients at index hospitalization were ultimately selected from the Nationwide Readmissions Database (NRD) 2018 to establish the 30-day and 180-day readmission cohorts, respectively. The study population was classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Multivariate Cox regression analysis was used to estimate the effect of metabolic obesity phenotypes on DSC readmission. Results: The MUNO phenotype had 1.147-fold (95% CI: 1.066, 1.235; p < 0.001) increased 180-day readmission risks in patients with neoplasm of the upper digestive tract. The MUNO phenotype had 1.073-fold (95% CI: 1.027, 1.121; p = 0.002) increased 30-day readmission risks and 1.067-fold (95% CI: 1.021, 1.115; p = 0.004) increased 180-day readmission risks in patients with neoplasm of the lower digestive tract. The MUNO and MUO phenotypes were independent risk factors of readmission in patients with liver or pancreatic neoplasm. Metabolic obesity status was independently associated with a high risk of severe and unplanned hospitalization within 30 days or 180 days. Conclusion: Both obesity and metabolic abnormalities are associated with a high risk for the poor prognosis of DSC patients. The effect of metabolic categories on the short- or long-term readmission of liver or pancreas cancers may be stronger than that of obesity.

Abdominal obesity and digestive system cancer: a systematic review and meta-analysis of prospective studies.

BACKGROUND: The diagnostic criteria for abdominal obesity are usually waist circumference or waist-to-hip ratio. The magnitude of the risks for cancers of the digestive system and abdominal obesity is unknown. To assess whether abdominal obesity increases the risk of digestive cancer, we conducted a systematic review and meta-analysis of prospective cohort studies in a database. METHODS: PubMed, Embase, and Web of Science databases were searched from their inception to December 2022. The 9-star Newcastle Ottawa Scale was used to assess  study quality. Pooled relative risks and 95% confidence intervals were calculated using fixed or random effect models respectively. The stability of the results was explored by one-by-one exclusion. Subgroup analysis was conducted to explore sources of heterogeneity. Publication bias was evaluated by Begg's and Egger's tests. RESULTS: A total of 43 cohort studies were included. There were 42 and 31 studies in the meta-analysis of waist circumference and waist-to-hip ratio on digestive system cancer, respectively. The results of the meta-analysis revealed that the greater waist circumference and waist-to-hip ratio were correlated with increased incidence of digestive system cancers: waist circumference: RR 1.48, 95% CI 1.38-1.59, p < 0.001; waist-to-hip ratio: RR 1.33, 95% CI 1.28-1.38, p = 0.001. Subgroup analysis by cancer type showed that higher WC and WHR would increase the prevalence of LC, PC, GC, EC, and CRC. The sensitivity analysis was conducted by a one-by-one elimination method, and the results of the meta-analysis remained stable. It is proved that the results were robust by the trim-and-fill method. CONCLUSIONS: There was evidence to suggest that abdominal obesity increased the incidence of digestive cancer, it is necessary to take appropriate measures to reduce abdominal obesity. Waist circumference and waist-to-hip ratio may be better predictors of digestive system cancers. However, the association between waist circumference and digestive system cancer was greater, so more attention should be paid to measuring abdominal obesity with waist circumference.

Association between diabetes at different diagnostic ages and risk of cancer incidence and mortality: a cohort study.

Background: Different ages for diagnosis of diabetes have diverse effects on risks of cardiovascular disease, dementia, and mortality, but there is little evidence of cancer. This study investigated the relationship between diabetes at different diagnostic ages and risks of cancer incidence and mortality in people aged 37-73 years. Methods: Participants with diabetes in the UK Biobank prospective cohort were divided into four groups: ≤40, 41-50, 51-60, and >60 years according to age at diagnosis. A total of 26,318 diabetics and 105,272 controls (1:4 randomly selected for each diabetic matched by the same baseline age) were included. We calculated the incidence density, standardized incidence, and mortality rates of cancer. Cox proportional hazard model was used to examine the associations of diabetes at different diagnostic ages with cancer incidence and mortality, followed by subgroup analyses. Results: Compared to corresponding controls, standardized incidence and mortality rates of overall and digestive system cancers were higher in diabetes diagnosed at age 41-50, 51-60, and >60 years, especially at 51-60 years. Individuals diagnosed with diabetes at different ages were at higher risk to develop site-specific cancers, with a prominently increased risk of liver cancer since the diagnosis age of >40 years. Significantly, participants with diabetes diagnosed at 51-60 years were correlated with various site-specific cancer risks [hazard ratio (HR) for incidence: 1.088-2.416, HR for mortality: 1.276-3.269]. Moreover, for mortality of digestive system cancers, we observed an interaction effect between smoking and diabetes diagnosed at 51-60 years. Conclusion: Our findings highlighted that the age at diagnosis of diabetes, especially 51-60 years, was critical risks of cancer incidence and mortality and may represent a potential preventative window for cancer.

Risk of chronic liver disease and cirrhosis mortality among patients with digestive system cancers: a registry-based analysis.

Non-cancer deaths are now becoming a great threat to the health of cancer survivors. There are no comprehensive and systematic reports on chronic liver disease and cirrhosis mortality (CLDCM) among patients with digestive system cancers (DSCs). This research aimed to quantitatively assess the risks and patterns of CLDCM among patients with DSCs. From the surveillance, epidemiology and end results (SEER) program, we extracted the data of patients diagnosed with DSCs between 2000 and 2017. Trends in incidence-based mortality rate (IBMR) were calculated using Joinpoint software. The standardized mortality ratio (SMR) was obtained based on the reference of the general United States population. The cumulative incidence function curves were constructed by all causes of death. Independent indicators were identified using the multivariate Fine and Gray competing risk model. We included 906,292 eligible patients from the SEER program, of which 3068 (0.34%) died from chronic liver disease and cirrhosis (CLDC). The IBMR of CLDC continued to increase during the study period [average annual percent change (APC): 6.7%; 95% confidence interval (CI) 5.1-8.2] and the SMR was significantly increased (SMR: 3.19; 95% CI 3.08-3.30). The cumulative mortality of CLDC was the lowest in all causes of death. Furthermore, the age at diagnosis, race, gender, marital status, year of diagnosis, SEER stage, surgery, chemotherapy and radiotherapy were identified as independent indicators. Better screening, diagnostic and management approaches need to be implemented as a preferred method to protect the liver among patients with DSCs.

Laparoscopic resection for gastric schwannoma larger than 30 mm with long-term outcomes.

BACKGROUND AND AIMS: Laparoscopic resection has been reported as effective and safe for gastric schwannoma (GS) in the form of case reports. However, study on laparoscopic surgery in patients with GS larger than 30 mm has been rarely reported. To this end, the present study aimed to evaluate the safety and efficacy of laparoscopic resection for the treatment of GS larger than 30 mm and its long-term outcomes. METHODS: This is a retrospective case series study of patients with GS larger than 30 mm who underwent laparoscopic resection at our hospital between January 2014 and December 2020. Clinical pathology, surgical and follow-up data were collected and analyzed. RESULTS: A total of 10 patients with a mean age of 51.6 years were included. Seven tumors were located in gastric body, 2 in antrum and 1 in fundus. Laparoscopic gastric wedge resection was performed in 7 patients, while laparoscopic gastric local resection was performed in 3 patients. All patients achieved complete resection. The mean operation time was 112.6 ± 34.3 min, and the mean postoperative hospital stay was 13.8 ± 5.1 days. Postoperative gastroplegia occurred in 2 patients and was treated with conservative therapy. No recurrence, metastasis or residue was found during the follow-up of mean 45.1 months. CONCLUSIONS: Laparoscopic resection is a safe and effective method for treating GS larger than 30 mm with favorable long-term follow-up outcomes. Laparoscopic resection may be considered as the first-line treatment for GS larger than 30 mm.

Clinicopathological characteristics and its association with digestive system tumors of 1111 patients with Schistosomiasis japonica.

Schistosomiasis japonicum can cause different degrees of organ damage and complex human immune pathological reactions, which often invade the intestine and liver. The purpose of this study was to explore the pathological types and pathological changes of Schistosomiasis and their correlation with some digestive system tumors. Hematoxylin eosin staining was performed on the diseased tissues of 1111 Schistosomiasis cases. We counted the deposition sites of Schistosoma eggs, analyzed the pathological characteristics, and compared the clinicopathological characteristics of Schistosomiasis associated digestive system tumors and non-Schistosomiasis digestive system tumors. We found that Schistosoma japonicum can cause multi organ and multi system damage, with 469 cases of inflammation, 47 cases of adenoma, and 519 cases of adenocarcinoma. Other types include cysts, stromal tumors, malignant lymphomas, and neuroendocrine tumors. Schistosomiasis associated tumors, including gastric cancer, liver cancer, colon cancer and rectal cancer, were compared with non-Schistosomiasis tumors. There were significant differences in age, gender and tumor differentiation between the two groups. Our study shows Schistosomiasis is a systemic disease, causing multiple organ and system damage in the human body. Its clinicopathological types are diverse, and there may be a pathological change process of "Inflammation-adenoma-carcinoma". Schistosomiasis associated digestive system tumors differ from non-Schistosomiasis tumors in some clinicopathological features.