Abstract

BackgroundGastric cancer (GC) still represents the third leading cause of cancer-related death worldwide. Peritoneal relapse (PR) is the most frequent metastasis occurring among patients with advanced gastric cancer. Increasingly more evidence have clarified the tumor immune microenvironment (TIME) may predict survival and have clinical significance in GC. However, tumor-transcriptomics based immune signatures derived from immune profiling have not been established for predicting the peritoneal recurrence of the advanced GC.MethodsIn this study, we depict the immune landscape of GC by using transcriptome profiling and clinical characteristics retrieved from GSE62254 of Gene Expression Omnibus (GEO). Immune cell infiltration score was evaluated via single-sample gene set enrichment (ssGSEA) analysis algorithm. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used to select the valuable immune cells and construct the final model for the prediction of PR. The receiver operating characteristic (ROC) curve and the Kaplan-Meier curve were used to check the accuracy of PRIs. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to explore the molecular pathways associated with PRIs.ResultsA peritoneal recurrence related immune score (PRIs) with 10 immune cells was constructed. Compared to the low-PRIs group, the high-PRIs group had a greater risk. The upregulation of the focal adhesion signaling was observed in the high-PRIs subtype by GSEA and KEGG. Multivariate analysis found that both in the internal training cohort and the internal validation cohort, PRIs was a stable and independent predictor for PR. A nomogram that integrated clinicopathological features and PRIs to predict peritoneal relapse was constructed. Subgroup analysis indicated that the PRIs could obviously distinguish peritoneal recurrence in different molecular subtypes, pathological stages and Lauren subtypes, in which PRIs of Epithelial-Mesenchymal Transitions (EMT) subtype, III-IV stage and diffuse subtype are higher respectively.ConclusionOverall, we performed a comprehensive evaluation of the immune landscape of GC and constructed a predictive PR model based on the immune cell infiltration. The PRIs represents novel promising feature of predicting peritoneal recurrence of GC and sheds light on the improvement of the personalized management of GC patients after surgery.

Highlights

  • Gastric cancer (GC) ranks the fifth in prevalent lethal malignancies and the third in cancer-related death worldwide [1]

  • In order to clarify the effect of Peritoneal relapse (PR) on the overall survival (OS) and progression free survival (PFS) of gastric cancer patients after surgery, we verified it in GSE62254 cohort. 300 patients were divided into PR- and PR+ groups according to their PR status after surgery

  • We verified the infiltration scores of 24 types of immune cells in PR+ and PR- groups in GSE15081, and the results were (Supplement Figure 1B). This makes us realize that immune cells may play an important role in PR, and the infiltration of immune cells can reflect the PR of patients

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Summary

Introduction

Gastric cancer (GC) ranks the fifth in prevalent lethal malignancies and the third in cancer-related death worldwide [1]. Of the patients with advanced-stage GC, most of them develop liver, lymph nodes and peritoneum metastasis within 5 years after radical surgery. Among these metastases, peritoneal dissemination is the most frequent and lethal, especially in the serosa-invasive gastric cancers [2]. Gastric cancer (GC) still represents the third leading cause of cancerrelated death worldwide. Peritoneal relapse (PR) is the most frequent metastasis occurring among patients with advanced gastric cancer.

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