Inflammatory response in gastrointestinal cancers:Overview of six transmembrane epithelial antigens of the prostate in pathophysiology and clinical implications

Chronic inflammation is known to increase the risk of gastrointestinal cancers(GICs),the common solid tumors worldwide.Precancerous lesions,such as chronic atrophic inflammation and ulcers,are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis.Unfortunately,due to the lack of effective therapeutic targets,the prognosis of patients with GICs is still unsatisfactory.Interestingly,it is found that six transmembrane epithelial antigens of the prostate(STEAPs),a group of metal reductases,are significantly associated with the progression of malignancies,playing a crucial role in systemic metabolic homeostasis and inflammatory responses.The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress,responding to inflammatory reactions.Under the imbalance status of abnormal oxidative stress,STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process.This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms,with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.

Roles of cancer stem cells in gastrointestinal cancers

Cancer stem cells(CSCs)are the main cause of tumor growth,invasion,metastasis and recurrence.Recently,CSCs have been extensively studied to identify CSCspecific surface markers as well as signaling pathways that play key roles in CSCs self-renewal.The involvement of CSCs in the pathogenesis of gastrointestinal(GI)cancers also highlights these cells as a priority target for therapy.The diagnosis,prognosis and treatment of GI cancer have always been a focus of attention.Therefore,the potential application of CSCs in GI cancers is receiving increasing attention.This review summarizes the role of CSCs in GI cancers,focusing on esophageal cancer,gastric cancer,liver cancer,colorectal cancer,and pancreatic cancer.In addition,we propose CSCs as potential targets and therapeutic strategies for the effective treatment of GI cancers,which may provide better guidance for clinical treatment of GI cancers.

Comprehensive analysis of cell-extracellular matrix protein Ras suppressor-1 in function and prognosis of gastrointestinal cancers

BACKGROUND Ras suppressor 1(RSU1),a highly conserved protein,plays an important role in actin cytoskeleton remodeling and cell-extracellular matrix adhesion.Aberration of RSU1 activity can cause changes in cell adhesion and migration,thereby enhancing tumor proliferation and metastasis.However,the correlation between RSU1 and gastrointestinal cancers(GICs),as well as its prognostic role related to tumor-infiltrating immune cells(TIICs)remains unclear.AIM To shows RSU1 plays a potential promoting role in facilitating tumor immune escape in GIC.METHODS Differential expression of RSU1 in different tumors and their corresponding normal tissues was evaluated by exploring the Gene Expression Profiling Interactive Analysis(GEPIA)dataset.The correlation between RSU1 expression and prognosis of GIC cancer patients was evaluated by Kaplan-Meier plotter.Then,RSU1-correlated genes were screened and functionally characterized via enrichment analysis.The correlation between RSU1 and TIICs was further characterized using the Tumor Immune Estimation Resource(TIMER).In addition,the correlation between RSU1 and immune cell surface molecules was also analyzed by TIMER.RESULTS High RSU1 expression was associated with poor overall survival of gastric cancer patients,exhibiting a hazard ratio(HR)=1.36,first progression HR=1.53,and post progression survival HR=1.6.Specifically,high RSU1 Levels were associated with prognosis of gastric cancer in females,T4 and N3 stages,and Her-2-negative subtypes.Regarding immune-infiltrating cells,RSU1 expression level was positively correlated with infiltration of CD4+T cells,macrophages,neutrophils,and dendritic cells(DCs)in colorectal adenocarcinoma and stomach adenocarcinoma.RSU1 expression was also predicted to be strongly correlated with immune marker sets in M2 macrophage,DCs and T cell exhaustion in GICs.CONCLUSION In gastrointestinal cancers,RSU1 is increased in tumor tissues,and predicts poor survival of patients.Increased RSU1 may be involved in promoting macrophage polarization,DC infiltration,and T cell exhaustion,inducing tumor immune escape and the development of tumors in GICs.We suggest that RSU1 is a promising prognostic biomarker reflecting immune infiltration level of GICs,as well as a potential therapeutic target for precision treatment through improving the immune response.

Recent advances in gastrointestinal cancers

Gastrointestinal cancers occur in a total of eight different locations,each of them with a different standard of care.This article is not an exhaustive review of what has been published in 2020.We have concentrated on the thirteen phase III randomized studies that are practice-changing.All these studies are oral presentations which have been given in one of the four major oncology congresses,namely American Society of Clinical Oncology(ASCO),ASCO gastrointestinal(GI),European Society of Medical Oncology(ESMO)and ESMO-GI.We provide a concise view of these major trials and their main outcomes,and put these results into context.

Photodynamic Therapy for Upper Gastrointestinal Cancers during Past 25 Years in China

Objective： To evaluate the status of photodynamic therapy （PDT） for upper gastrointestinal cancers, and then discuss how to solve the problems that hinder the development of PDT. Methods： A total of 30 pertinent literatures about PDT for upper gastrointestinal cancers during past 25 years were collected through the retrieval of several related medical databases （Chinese Medical Current Contents, China Bio-Medical Bibliographic Database, China Journal Fulltext Database）. The data, including the gender, age of patients, tumor position, pathologic findings, treatment efficacy, adverse effects and the applied laser and photosensitizer, were statistically analyzed. Results： For all the 1687 cases with upper gastrointestinal cancers, the excellent-effective rate （complete remission or prominent remission） and effective rate （complete remission or prominent remission or minor remission） were 53.2% and 87%, respectively. The therapeutic effect of combined treatment （PDT with other methods） was superior to that of PDT （u=4.456, P〈0.01）. All the involved pathological types were sensitive to PDT. Different photosensitizers and lasers were used by different authors, but all of them were effective without any serious side effect. Conclusion： PDT shows a radical effect on the tumors of early stage and a favorable palliative effect on the tumors of advanced stage, so it is one of the optional strategies for the treatment of upper gastrointestinal cancers.

Systems biology and OMIC data integration to understand gastrointestinal cancers

Gastrointestinal(GI)cancers are a set of diverse diseases affecting many parts/organs.The five most frequent GI cancer types are esophageal,gastric cancer(GC),liver cancer,pancreatic cancer,and colorectal cancer(CRC);together,they give rise to 5 million new cases and cause the death of 3.5 million people annually.We provide information about molecular changes crucial to tumorigenesis and the behavior and prognosis.During the formation of cancer cells,the genomic changes are microsatellite instability with multiple chromosomal arrangements in GC and CRC.The genomically stable subtype is observed in GC and pancreatic cancer.Besides these genomic subtypes,CRC has epigenetic modification(hypermethylation)associated with a poor prognosis.The pathway information highlights the functions shared by GI cancers such as apoptosis;focal adhesion;and the p21-activated kinase,phosphoinositide 3-kinase/Akt,transforming growth factor beta,and Toll-like receptor signaling pathways.These pathways show survival,cell proliferation,and cell motility.In addition,the immune response and inflammation are also essential elements in the shared functions.We also retrieved information on protein-protein interaction from the STRING database,and found that proteins Akt1,catenin beta 1(CTNNB1),E1A binding protein P300,tumor protein p53(TP53),and TP53 binding protein 1(TP53BP1)are central nodes in the network.The protein expression of these genes is associated with overall survival in some GI cancers.The low TP53BP1 expression in CRC,high EP300 expression in esophageal cancer,and increased expression of Akt1/TP53 or low CTNNB1 expression in GC are associated with a poor prognosis.The Kaplan Meier plotter database also confirmed the association between expression of the five central genes and GC survival rates.In conclusion,GI cancers are very diverse at the molecular level.However,the shared mutations and protein pathways might be used to understand better and reveal diagnostic/prognostic or drug targets.

Myeloid-derived suppressor cells in gastrointestinal cancers:A systemic review

Gastrointestinal(GI)cancers are one of the most common malignancies worldwide,with high rates of morbidity and mortality.Myeloid-derived suppressor cells(MDSCs)are major components of the tumor microenvironment(TME).MDSCs facilitate the transformation of premalignant cells and play roles in tumor growth and metastasis.Moreover,in patients with GI malignancies,MDSCs can lead to the suppression of T cells and natural killer cells.Accordingly,a better understanding of the role and mechanism of action of MDSCs in the TME will aid in the development of novel immune-targeted therapies.

Correlations between P2RX1 Expression and Gastrointestinal Cancers Prognosis and Immune Infiltration Based on Bioinformatics Analysis

This study was conducted to explore the correlations between the expression,methylation,and various clinicopathological factors of purinergic P2X1 receptor(P2RX1)and the prognosis of patients with gastrointestinal tumors.The Cancer Genome Atlas(TCGA)and the Genotype-Tissue Expression(GTEx)databases were used to analyze the expression of P2RX1 in different types of gastrointestinal cancers.Kaplan-Meier analysis and univariate Cox regression analysis were used to analyze the correlations between P2RX1 expression and the prognosis of various gastrointestinal tumors.Correlations between P2RX1 expression and N6 methyladenine(m6A)-related genes as well as immune checkpoint genes were analyzed by R packages(R version:4.0.3)based on TCGA database.The association between P2RX1 methylation level and the prognosis of patients with gastrointestinal cancers was analyzed using the MethSurv database.In order to explore the biological functions of P2RX1 in hepatocellular carcinoma,the Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analysis were carried out using R software.In order to evaluate the correlations between P2RX1 and tumor immune infiltration,Spearman correlation test was performed.The correlations between P2RX1 expression and immune score as well as immune checkpoint genes were analyzed based on TCGA and Tumor Immune Estimation Resource(TIMER)databases.The expression of P2RX1 was found to be significantly downregulated in gastrointestinal tumors except in cholangiocarcinoma(P<0.05).High expression of P2RX1 tended to present better prognosis in hepatocellular carcinoma(P<0.05).It was noted that cg06475633 of P2RX1 presented a higher methylation level compared with other CpG sites in hepatocellular carcinoma.Overall,six CpGs of P2RX1 were associated with significant prognosis in patients with hepatocellular carcinoma(P<0.05).Among all the 20 m6A-related genes,Wilms'tumor 1-associating protein(WTAP)was the most strongly correlated with P2RX1 in hepatocellular carcinoma.Gene enrichment analysis showed that P2RX1 is widely involved in the proliferation,activation,organization,and differentiation of various immune cells.After investigating the TIMER database,P2RX1 was found to be tightly correlated with immune infiltrating cells in gastrointestinal tumors,especially with dendritic cells.Moreover,P2RX1 was found to be strongly positively associated with programmed cell death 1(PD1),programmed death-ligand 1(PD-L1),and cytotoxic T-lymphocyte-associated protein 4(CTLA4)in hepatocellular carcinoma(P<0.05).In conclusion,the dual role of P2RX1 in cancers and its involvement in the recruitment as well as regulation of tumor infiltrating cells in gastrointestinal cancers may be appreciated through this study.

Role of Ubiquitin-Conjugating Enzyme UBE2C in Gastrointestinal Cancers

Ubiquitin-conjugating enzyme UBE2C is one of the important members of ubiquitin-proteasome pathway(UPP).Amplification and/or overexpression of UBE2C have been reported in many malignancies,and a high expression of UBE2C is associated with poor clinical outcomes.In this review,the pathological role of dysregulated UBE2C in gastrointestinal cancers and its potential role as a diagnostic and/or a prognostic marker as well as a therapeutic target in these cancers are discussed.

Regulatory role of the transforming growth factor-β signaling pathway in the drug resistance of gastrointestinal cancers

Gastrointestinal(GI)cancer,including esophageal,gastric,and colorectal cancer,is one of the most prevalent types of malignant carcinoma and the leading cause of cancer-related deaths.Despite significant advances in therapeutic strategies for GI cancers in recent decades,drug resistance with various mechanisms remains the prevailing cause of therapy failure in GI cancers.Accumulating evidence has demonstrated that the transforming growth factor(TGF)-βsignaling pathway has crucial,complex roles in many cellular functions related to drug resistance.This review summarizes current knowledge regarding the role of the TGF-βsignaling pathway in the resistance of GI cancers to conventional chemotherapy,targeted therapy,immunotherapy,and traditional medicine.Various processes,including epithelial-mesenchymal transition,cancer stem cell development,tumor microenvironment alteration,and microRNA biogenesis,are proposed as the main mechanisms of TGF-β-mediated drug resistance in GI cancers.Several studies have already indicated the benefit of combining antitumor drugs with agents that suppress the TGF-βsignaling pathway,but this approach needs to be verified in additional clinical studies.Moreover,the identification of potential biological markers that can be used to predict the response to TGF-βsignaling pathway inhibitors during anticancer treatments will have important clinical implications in the future.

Radiofrequency Ablation Combined with Transarterial Chemoembolization for Liver Metastases from Gastrointestinal Cancers

Transarterial chemoembolization（TACE） combined with radiofrequency ablation（RFA） has been reported to be effective for local control of different-sized hepatocellular carcinomas. However, it is unclear if these benefits could also be applicable to different-sized liver metastases from gastrointestinal cancers. The aim of this study was to evaluate the outcomes of TACE combined with RFA for liver metastases from gastrointestinal cancers. In this study, we retrospectively analyzed clinical data of 19 consecutive patients who had a total of 26 liver metastatic lesions from gastrointestinal cancers and underwent RFA followed by first-time TACE treatment. The tumor recurrence, overall survival rate and procedure-related complications were evaluated. Moreover, patients＇ demographics and tumor characteristics were analyzed to determine their impact on the outcomes. The technical success of TACE plus RFA was achieved with 2 major procedure-related complications found. The mean follow-up was 21.3 months. The total 1-, 2-, and 3-year survival rate was 89.4%, 52.6%, and 35.1%, respectively. It was found that the tumor size and the ratio of enhancement area were significant factors that influenced the overall survival. In conclusion, patients with gastrointestinal cancer-derived liver metastatic lesions of smaller size and larger enhancement area are considered appropriate candidates for TACE plus RFA.

Biomarkers for response to immune checkpoint inhibitors in gastrointestinal cancers

Gastrointestinal(GI)cancers account for a large proportion of cancer deaths worldwide and pose a major public health challenge.Immunotherapy is considered to be one of the prominent and successful approaches in cancer treatment in recent years.Among them,immune checkpoint inhibitor(ICI)therapy,has received widespread attention,and many clinical findings support the feasibility of ICIs,with sustained responses and significantly prolonged lifespan observed in a wide range of tumors.However,patients treated with ICIs have not fully benefited,and therefore,the identification and development of biomarkers for predicting ICI treatment response have received further attention and exploration.From tumor genome to molecular interactions in the tumor microenvironment,and further expanding to circulating biomarkers and patient characteristics,the exploration of biomarkers is evolving with high-throughput sequencing as well as bioinformatics.More large-scale prospective and specific studies are needed to explore biomarkers in GI cancers.In this review,we summarize the known biomarkers used in ICI therapy for GI tumors.In addition,some ICI biomarkers applied to other tumors are included to provide insights and further validation for GI tumors.Moreover,we present single-cell analysis and machine learning approaches that have emerged in recent years.Although there are no clear applications yet,it can be expected that these techniques will play an important role in the application of biomarker prediction.

Upper Gastrointestinal Cancers in Rwanda: Epidemiological, Clinical and Histopathological Features in Patients Presenting to a Tertiary Referral Hospital

Background: Scant data on upper gastrointestinal cancers in Rwanda exist to guide potential prevention efforts. We evaluated the epidemiological, clinical and histopathological data among patients with gastric and esophageal tumors at a tertiary Referral Hospital in Rwanda. Methodology: We performed a retrospective review of histologically-confirmed esophageal and gastric cancers in adults age ≥ 18 yrs. old presenting to a university teaching hospital (Centre Hospitalier Universitaire de Butare) from 2014-2019. Variables included age at diagnosis, sex, clinical presentation, tumor location and histopathological type. Results: There were 149 upper gastrointestinal cancers, of which 137 (92%) were gastric and 12 (8%) were esophageal. Gastric cancer patients had a mean age at presentation of 56.9 ± 12.3 years (range 21 - 87). Presenting symptoms were epigastric pain (78.8%), weight loss (53.3%), post-prandial vomiting (52.6%), early satiety (29.9%), epigastric mass (24.8%), hematemesis (19.7%) and melena (16.8%). The location was antrum 50.3%, corpus 21.8%, fundus 8%, and cardia 8%. Tumor type was adenocarcinoma in 94.1%. Helicobacter pylori infection was present in 108 (78.8%). Esophageal cancer patients had a mean age of 54.4 ± 9.5 years (range 35 - 72). Presenting symptoms were dysphagia (100%) and weight loss (83%). The most common site was lower third esophagus (9/12), and adenocarcinoma cancer subtype accounted for 5/12 (41.6%) cases. Conclusion: Gastric adenocarcinoma was the most commonly diagnosed upper gastrointestinal cancers and was associated with a high prevalence of H. pylori infection. This study lays the foundation for future work to improve cancer outcomes in Rwanda.

Use of liquid biopsies in gastrointestinal cancers

The use of liquid biopsies is a relatively new tool in diagnosis and management of gastrointestinal cancers and is actively being investigated.Liquid biopsies have become extremely popular in cholangiocarcinoma and pancreatic cancer research.With more prospective trials using this tool for early diagnosis,liquid biopsies may become an important part of cancer management.

Bromodomain and extra-terminal inhibitors emerge as potential therapeutic avenues for gastrointestinal cancers

Gastrointestinal(GI)cancers,including colorectal cancer,pancreatic cancer,liver cancer and gastric cancer,are severe social burdens due to high incidence and mortality rates.Bromodomain and extra-terminal(BET)proteins are epigenetic readers consisting of four conserved members(BRD2,BRD3,BRD4 and BRDT).BET family perform pivotal roles in tumorigenesis through transcriptional regulation,thereby emerging as potential therapeutic targets.BET inhibitors,disrupting the interaction between BET proteins and acetylated lysines,have been reported to suppress tumor initiation and progression in most of GI cancers.In this review,we will demonstrate how BET proteins participate in the GI cancers progression and highlight the therapeutic potential of targeting BET proteins for GI cancers treatment.

Receptor tyrosine kinase-like orphan receptor 1:A novel antitumor target in gastrointestinal cancers

Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It has soluble and membrane-bound subtypes,with the latter highly expressed in tumors.ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms.Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis.Additionally,ROR1 may regulate the cell cycle,stem cell characteristics,and interact with other signaling pathways to affect cancer progression.This review explores the structure,expression and role of ROR1 in the development of gastrointestinal cancers.It discusses current antitumor strategies,outlining challenges and prospects for treatment.

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

Tata-box-binding protein-associated factor 15 as a new potential marker in gastrointestinal tumors

In this editorial,the roles of tata-box-binding protein-associated factor 15(TAF15)in oncogenesis,tumor behavior,and as a therapeutic target in cancers in the context of gastrointestinal(GI)tumors are discussed concerning the publication by Guo et al.TAF15 is a member of the FET protein family with a comprehensive range of cellular processes.Besides,evidence has shown that TAF15 is involved in many diseases,including cancers.TAF15 contributes to carcinogenesis and tumor behavior in many tumors.Besides,its relationship with the mitogen-activated protein kinases(MAPK)signaling pathway makes TAF15 a new target for therapy.Although,the fact that there is few studies investigating the expression of TAF15 constitutes a potential limitation in GI system,the association of TAF15 expression with aggressive tumor behavior and,similar to other organ tumors,the influence of TAF15 on the MAPK signaling pathway emphasize that this protein could serve as a new molecular biomarker to predict tumor behavior and target therapeutic intervention in GI cancers.In conclusion,more studies should be performed to better understand the prognostic and therapeutic role of TAF15 in GI tumors,especially in tumors resistant to therapy.

Early-onset gastrointestinal cancer:An epidemiological reality with great significance and implications

During the last few years,epidemiological data from many countries suggest that the incidence and prevalence of many cancers of the digestive system are shifting from the older to the younger ages,the so-called“early-onset cancer”.This is particularly evident in colorectal cancer and secondarily in other malignant digestive neoplasms,mainly stomach and in a lesser degree pancreas,and biliary tract.It should be emphasized that data concerning digestive neoplasms,except for those referring to the colon and stomach,could be characterized as rather insufficient.The exact magnitude of the shift in younger ages is expected to become clearer shortly,as long as relevant epidemiological data from many parts of the world would be available.The most important question concerns the etiology of this phenomenon,since its magnitude cannot be explained solely by the better diagnostic methodology and the preventive programs applied in many countries.The existing data support the assumption that a number of environ-mental factors may play a primary role in influencing carcinogenesis,sometimes from childhood.Changes that have appeared in the last decades related mainly to eating habits,consistency of gut microbiome and an increase of obese people interacting with genetic factors,ultimately favor the process of carcinogenesis.Even these factors however,are not entirely sufficient to explain the age-related changes in the frequency of digestive neoplasms.Studies of the individual effect of each of the already known factors or factors likely to be involved in the etiology of this phenomenon and studies using state-of-the-art technologies to accurately determine the degree of the population exposure to these factors are required.In this article,we attempt to describe the epidemiological data supporting the age-shifting of digestive malignancies and their possible pathogenesis.Finally,we propose some measures regarding the attitude of the scientific community to this alarming phenomenon.

Association of plant-based diets with the risk of upper gastrointestinal tract cancers:A systematic review and meta-analysis

Background:Diets rich in red or processed meat have been linked to an increased risk of cancers within the digestive system.It has been suggested that a plant-based diet may have protective effects against digestive system cancers.This study aimed to determine the association between plant-based diets and upper gastrointestinal tract cancers(UGTC).Methods:We conducted a systematic review and meta-analysis of observational studies.We searched the PubMed,Medline,Embase,and Web of Science databases for articles published up to September 30,2023.We pooled the risk ratios(RR)with the corresponding 95%confi-dence intervals(CI)using fixed or random-effects models.Results:Our meta-analysis included 16 studies(30 results).The data revealed a strong inverse association between a high intake of plant-based diets and UGTC(RR=0.60,95%CI=0.49-0.72),specifically gastric cancer(GC,RR=0.53,95%CI=0.42-0.67)and esophageal can-cer(EC,RR=0.63,95%CI=0.42-0.96).This relationship was not significant for gastric cardia cancer(GCA)or esophagogastric junctional cancer(EGJC,RR=0.76,95%CI=0.47-1.22).A subgroup analysis showed the association was significant in studies from Asia and Europe,as well as in studies utilizing indices such as a vegetarian diet,Mediterranean diet,the plant-based diet index,and principal component analy-sis(PCA)dietary patterns.There was no indication of publication bias among the analyzed studies.Conclusions:This meta-analysis highlights the potential health benefits of plant-based diets in preventing UGTC,particularly regarding esophageal squamous cell carcinoma(ESCC)and GC.Nevertheless,additional research is required to validate these results and explore the un-derlying mechanisms.