Genomic And Microbiome Features Of Locally Advanced Gastric Cancer,and The Construction And Validation Of Prognostic Prediction Models

Objective:Gastric cancer is one of the most common and deadliest malignant tumors worldwide,with over 1 million new cases and approximately 769,000 deaths in 2020.Globally,the incidence and mortality rates of gastric cancer rank fifth and fourth,respectively.According to the TNM staging,there is significant variation in the prognosis of patients with the same stage of gastric cancer.Therefore,this study aims to analyze the clinical pathological features,gene mutation features,and microbiome composition features in gastric cancer patients and to explore the factors related to gastric cancer patient prognosis.Methods:This study included 96 patients with locally advanced gastric cancer,and collected their surgical paraffin section samples,clinical pathological information,and follow-up information.The genomic mutation features were obtained by whole-exome sequencing,and the microbiome features were obtained by constructing a high-resolution microbial sequencing method.A prognostic prediction model was constructed by combining clinical pathological features,gene mutation features,and microbiome composition features,and the model was validated.Results:In this study,lymph node metastasis rate greater than 70%is an independent prognostic factor for overall survival(OS)in gastric cancer patients.The most frequently mutated genes in gastric cancer patients were TP53,TTN,ARID1A and so on,among which the mutation of the ARID1A gene was associated with a better prognosis in gastric cancer patients.In terms of microbiome composition,Proteobacteria,Actinobacteria,Firmicutes,Armatimonadetes,and Bacteroidetes were the five most common phyla in the tumor tissues of gastric cancer patients.Among them,the Gemella genus under the phylum Firmicutes was associated with a better prognosis in gastric cancer patients.The Planomicrobium genus under the phylum Firmicutes and the Arthrobacter genus under the phylum Actinobacteria were associated with a poorer prognosis in gastric cancer patients.In the training set of the disease-free survival(DFS)prediction model,the area under curve(AUC)values for predicting 1-year,2-year,3-year,5-year,and 10-year DFS were 0.81,0.81,0.84,0.89,and 0.93,respectively.In the validation set,the model achieved AUC values of 0.95,0.79,0.84,0.84,and 0.87 for predicting 1-year,2-year,3-year,5-year,and 10-year DFS,respectively.In the training set of the OS prediction model,the AUC values for predicting 1-year,2-year,3-year,5-year,and 10-year OS were 0.58,0.75,0.79,0.82,and 0.91,respectively.In the validation set,the model achieved AUC values of 0.89,0.80,0.90,0.83,and 0.76 for predicting 1-year,2-year,3-year,5-year,and 10-year OS,respectively.Conclusion:The combination of clinical pathological features,gene mutation features,and microbiome composition features can predict DFS and OS in gastric cancer patients,contributing to the optimization of treatment strategies for patients with locally advanced gastric cancer.