A novel immune-related gene signature predicts survival in esophageal squamous cell carcinoma

Tao Xu; Tianyang Dai; Peiyuan Zeng; Yunfen Guo; Kaiming He

doi:10.21037/tcr-20-2665

A novel immune-related gene signature predicts survival in esophageal squamous cell carcinoma

Transl Cancer Res. 2021 May;10(5):2354-2367. doi: 10.21037/tcr-20-2665.

Authors

Tao Xu¹, Tianyang Dai¹, Peiyuan Zeng¹, Yunfen Guo², Kaiming He¹

Affiliations

¹ Department of Thoracic Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou, China.
² Department of Laboratory Medicine, the Nanchong Central Hospital, Nanchong, China.

Abstract

Background: Immune-related genes (IRGs) are highly relevant to the progression and prognosis of esophageal squamous cell carcinoma (ESCC). A prognostic signature could be reliable in stratifying ESCC patients according to the risk score, which may help manage systematic treatments. In this study, a systematic and reliable immune signature was developed to estimate the prognostic stratification in ESCC.

Methods: Ribonucleic acid (RNA) expression data of 79 ESCC samples from the Cancer Genome Atlas (TCGA) database and 269 normal esophageal mucosal samples from the Genotype-Tissue Expression (GTEx) project database were downloaded from the University of California, Santa Cruz (UCSC) website to form a TCGA-GTEx dataset. First, we screened differentially expressed genes (DEGs) and then filtered IRGs based on the Immunology Database and Analysis Portal (ImmPort) database to obtain immune-related DEGs (IRDEGs). Next, a novel prognostic signature based on IRDEGs was developed using multivariable Cox analysis. Immune infiltration status was evaluated via single-sample gene set enrichment analysis (ssGSEA). ESCC tissues were grouped into three clusters in terms of immune infiltration (Immunity-L, Immunity-M, and Immunity-H) by applying an unsupervised hierarchical clustering algorithm. Finally, the samples were divided into high- and low-risk groups using the median of the risk score scores for GSEA pathway enrichment analysis in the three clusters.

Results: The prognostic signature based on IRDEGs (FCER1G, ISG20, and EGFR) performed moderately in prognostic predictions, with a concordance index (C-index) value of 0.73 [95% (confidence interval) CI: 0.63-0.84, P=2.02E-05] and an area under the curve (AUC) value of 0.817. The xenobiotic metabolism pathway was significantly enriched and up-regulated both in the high-risk group of the immunity-M and immunity-H clusters.

Conclusions: The novel immune-related prognostic signature we constructed has a good prognostic, predictive ability and can be used as an independent prognostic indicator. Our study provides clinicians with a quantitative tool to predict the probability of individual survival time and helps clinicians select targets for immunotherapies and individualized treatment strategies for ESCC patients.

Keywords: Esophageal squamous cell carcinoma (ESCC); immune-related genes (IRGs); immunotherapy.