Establishment of an Immune Cell Infiltration Score to Help Predict the Prognosis and Chemotherapy Responsiveness of Gastric Cancer Patients.

Quan Jiang,Yihong Sun,Chen Ding,Jie Sun,Yuanyuan Ruan,Zhaoqing Tang,Fenglin Liu,Hao Chen

doi:10.3389/fonc.2021.650673

Abstract

The immune microenvironment plays a critical role in tumor biology. The molecular profiles of immune components and related genes are of tremendous value for the study of primary resistance to immune checkpoint blockers (ICBs) for gastric cancer (GC) and serve as prognostic biomarkers to predict GC survival. Recent studies have revealed that tumor immune cell infiltration (ICI) is an indicator of the survival and responsiveness to chemotherapy in GC patients. Here, we describe the immune cell landscape based on the ESTIMATE and CIBERSORT algorithms to help separate GC into 3 ICI clusters using the unsupervised clustering method. Further in-depth analyses, such as differential expression gene (DEG) analysis and principal component analysis (PCA), help to establish an ICI scoring system. A low ICI score is characterized by an increased tumor mutation burden (TMB). The combination of the ICI score and TMB score better predicts the survival of GC patients. Analyses based on public and our own database revealed that the ICI scoring system could also help predict the survival and chemotherapy responsiveness of GC patients. The present study demonstrated that the ICI score may be an effective prognostic biomarker and predictive indicator for chemotherapy and immunotherapy.

Highlights

Gastric cancer (GC) is a heterogeneous disease that is found worldwide, and it is ranked as the fifth most common cancer and the third leading cause of cancer-related death worldwide [1]
The patients were divided into 3 cohorts based on the unsupervised clustering of 22 immune cells derived from the CIBERSORT algorithm in 3 GC datasets
We reviewed the details of infiltrating immune cells in each immune cell infiltration (ICI) cluster and found that anti-cancer immune cells, such as CD8 T cells, activated memory CD4 T cells and M1 macrophages, were elevated in ICI cluster A, and the volume of immuneregulating cell-like regulatory T cells (Tregs) was increased in ICI cluster C

Summary

Introduction

Gastric cancer (GC) is a heterogeneous disease that is found worldwide, and it is ranked as the fifth most common cancer and the third leading cause of cancer-related death worldwide [1]. As concluded in previous studies, only 30% of GC is diagnosed at an ICI Predict GC Chemotherapy Responsiveness early stage, and the 5-year survival for pTNM stage groups divided based on the American Joint Committee on Cancer (AJCC) is between 68 and 80% for stage I, 46 and 60% for stage II, and 30% for stage III and 5% for stage IV [2]. Based on the different phenotypes under the microscope, GC is traditionally divided into 3 major histological subtypes according to Lauren’s classification, namely, intestinal, diffuse and mixed types [4]. The most widely acknowledged pathological system is the World Health Organization (WHO) classification, which divides GC into four main types based on the predominant histological patterns: tubular adenocarcinoma, papillary adenocarcinoma, mucinous adenocarcinoma and poorly cohesive carcinoma [5]. The Cancer Genome Atlas (TCGA) project, which divides GC into four subtypes, EBV-positive (EBV), microsatellite-unstable (MSI), genomically stable (GS) and chromosomal instability (CIN), has attracted the most attention [6]

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Conclusion