Research Paper Volume 12, Issue 18 pp 17958—17975

Prognostic landscape of tumor-infiltrating immune cells and immune-related genes in the tumor microenvironment of gastric cancer

Shichao Zhang1, *, , Zhu Zeng1,2, *, , Yongfen Liu1, , Jiangtao Huang1, , Jinhua Long3, , Yun Wang1, , Xiaoyan Peng1,2, , Zuquan Hu1,2, , Yan Ouyang1, ,

  • 1 Immune Cells and Antibody Engineering Research Center of Guizhou Province, Key Laboratory of Biology and Medical Engineering, School of Biology and Engineering/School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, Guizhou, P.R. China
  • 2 Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 550025, Guizhou, P.R. China
  • 3 Affiliated Tumor Hospital, Guizhou Medical University, Guiyang 550004, Guizhou, P.R. China
* Equal contribution

Received: March 24, 2020       Accepted: June 4, 2020       Published: September 23, 2020      

https://doi.org/10.18632/aging.103519
How to Cite

Copyright: © 2020 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The tumor microenvironment is closely related to the progression and immune escape of tumor cells. Tumor-infiltrating immune cells (TIICs) and immune-related genes (IRGs) are indispensable components of the tumor microenvironment and have been demonstrated to be highly valuable in determining the prognosis of multiple cancers. To elucidate the prognostic value of TIICs and IRGs in gastric cancer, we conducted a comprehensive analysis focusing on the abundances of 22 types of TIICs and differentially expressed IRGs based on a dataset from The Cancer Genome Atlas (TCGA). The results showed that great composition differences in TIICs and immune cell subfractions were associated with survival outcomes in different stages. Additionally, 29 hub genes were characterized from 345 differentially expressed IRGs and found to be significantly associated with survival outcomes. Then, an independent prognostic indicator based on ten IRGs was successfully constructed after multivariate adjustment for some clinical parameters. Further validation revealed that these hub IRGs could reflect the infiltration levels of immune cells. Thus, our results confirmed the clinical significance of TIICs and IRGs in gastric cancer and may establish a foundation for further exploring immune cell and gene targets for personalized treatment.

Abbreviations

TIICs: tumor-infiltrating immune cells; IRGs: immune-related genes; TCGA: The Cancer Genome Atlas; TME: tumor microenvironment; DEGs: differentially expressed genes; OS: overall survival; LASSO: least absolute shrinkage and selection operator; CAR-T: chimeric antigen receptor T cells; NK: natural killer; TILs: tumor-infiltrating lymphocytes; TAMs: tumor associated macrophages; Tregs: regulatory T cells; Tfh: follicular helper T cells; CTL: cytotoxic T lymphocyte; CTLA-4: CTL associated antigen 4; PD-1: programmed death 1; ERK: extracellular regulated protein kinases; FDR: false discovery rate; ROC: receiver operating characteristic; AUC: area under the ROC curve; HR: hazard ratio; CI: confidence interval; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes.