Esophageal Cancer Associated Immune Genes as Biomarkers for Predicting Outcome in Upper Gastrointestinal Tumors.

Chuanhui Zhu,Siyuan Shen,Dan Meng,Hua Jin,Wenjing Yan,Shuqian Xie,Xueliang Li,Bin Gu,Mengjing Cui,Qianqian Xia,Xing Zhang,Shizhi Wang

doi:10.3389/fgene.2021.707299

Abstract

Esophageal cancer (EC) is the seventh most common tumor in the world, ranking the sixth leading cause of cancer death, with a 5-year survival rate of 15-25%. Therefore, reliable prognostic biomarkers are needed to effectively predict the prognosis of EC. In this study, the gene profile information of the EC cohort served as a training set, which was derived from TCGA and Immport databases. GO and KEGG enrichment analysis was performed on the differential genes in normal and tumor groups of EC. The immune genes in differentially expressed genes (DEGs) were further obtained for univariate and multivariate Cox and Lasso regression analysis, and 6 independent immune genes (S100A3, STC2, HSPA6, CCL25, GPER1, and OSM) associated with prognosis were obtained to establish an immune risk score signature (IRSS). The signature was validated using head and neck cancers (HNSC) and gastric cancer (GC)in upper gastrointestinal malignancies as validation sets. The Kaplan-Meier results showed that the prognosis of the high-risk group was significantly favorable than that of the low-risk group in both the training set (P < 0.001; HR = 3.68, 95% CI = 2.14−6.35) and the validation set (P = 0.010; HR = 1.43, 95% CI = 1.09−1.88). A nomogram combining multiple clinical information and IRSS was more effective than a single independent prognostic factor in predicting outcome. This study explored the potential link between immunity and EC, and established and validated prognostic biomarkers that can effectively predict the prognosis of EC, HNSC and GC based on six immune genes.

Highlights

Esophageal cancer (EC) is the 7th most common tumor in the world (Global Burden of Disease Cancer Collaboration et al, 2018), ranking the 6th leading cause of cancer death, which seriously threatens human health (Bray et al, 2018)
Owing to the lack of early-onset symptoms, EC is usually diagnosed at an advanced stage
A major mechanism of inflammation-induced esophageal carcinogenesis is through structural activation of inflammatory signaling pathways (AbdelLatif et al, 2009)

Summary

Introduction

Esophageal cancer (EC) is the 7th most common tumor in the world (Global Burden of Disease Cancer Collaboration et al, 2018), ranking the 6th leading cause of cancer death, which seriously threatens human health (Bray et al, 2018). Biomarkers of Prognosis in Upper Gastrointestinal Tumors. Most patients are already at an advanced stage at diagnosis, the curative ratio is low and the prognosis is poor (Ferlay et al, 2015). Despite the application of new diagnostic and therapeutic techniques that have improved the survival rate of EC patients (Vendrely et al, 2018), the 5-year overall survival (OS) rate is still unsatisfactory, fluctuating between 15 and 25% (Short et al, 2017). It is urgent to find robust biomarkers to predict the prognosis of EC patients and provide potential therapeutic targets

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