Gene expression patterns associated with tumor-infiltrating CD4+ and CD8+ T cells in invasive breast carcinomas

Zhanwei Wang,Xi Yang,Junjun Shen,Jiamin Xu,Mingyue Pan,Jin Liu,Shuwen Han

doi:10.1016/j.humimm.2021.02.001

Abstract

BackgroundBreast carcinoma is one of the most common tumors in women. The immune microenvironment, especially T cell infiltration, is related to the occurrence and prognosis of breast carcinoma. ObjectiveThis study investigated the gene expression patterns associated with tumor-infiltrating CD4+ and CD8+ T cells in invasive breast carcinomas. MethodsThe gene expression data and corresponding clinical phenotype data from the Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) were downloaded. The stromal and immune score were calculated using ESTIMATE. The differentially expressed genes (DEGs) with a high vs. low stromal score and a high vs. low immune score were screened and then functionally enriched. The tumor-infiltrating immune cells were investigated using the Cibersort algorithm, and the CD4+ and CD8+ T cell-related genes were identified using a Spearman correlation test of infiltrating abundance with the DEGs. Moreover, the miRNA-mRNA pairs and lncRNA-miRNA pairs were predicted to construct the competing endogenous RNAs (ceRNA) network. Kaplan-Meier (K-M) survival curves were also plotted. ResultsIn total, 478 DEGs with a high vs. low stromal score and 796 DEGs with a high vs. low immune score were identified. In addition, 39 CD4+ T cell-related genes and 78 CD8+ T cell-related genes were identified; of these, 14 genes were significantly associated with the prognosis of BRCA patients. Moreover, for CD4+ T cell-related genes, the chr22-38_28785274-29006793.1–miR-34a/c-5p–CAPN6 axis was identified from the ceRNA network, whereas the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis was identified for CD8+ T cell-related genes. ConclusionsThe chr22-38_28785274-29006793.1–miR-34a/c-5p–CAPN6 axis and the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis might regulate cellular activities associated with CD4+ and CD8+ T cell infiltration, respectively, in BRCA.

Highlights

Breast carcinoma is one of the most common tumors in women, accounting for approximately 25% of all cancers; it is the second leading cause of cancer-related death in women worldwide [1]
For CD4 + T cell-related genes, the chr22-38_28785274-29006793.1–miR-34a/c-5p–CAPN6 axis was identified from the competing endogenous RNAs (ceRNA) network, whereas the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis was identified for CD8 + T cell-related genes
The chr22-38_28785274-29006793.1–miR-34a/c-5p–CAPN6 axis and the chr2238_28785274-29006793.1–miR-494-3p–SLC9A7 axis might regulate cellular activities associated with CD4 + and CD8 + T cell infiltration, respectively, in breast carcinoma (BRCA)

Summary

Introduction

Breast carcinoma is one of the most common tumors in women, accounting for approximately 25% of all cancers; it is the second leading cause of cancer-related death in women worldwide [1]. The clinical course and outcome of breast carcinoma differs with diverse immunohistochemical characteristics and histopathological subtypes [3]. The therapeutic prospects of malignancies, including breast carcinomas, have been remarkably altered with a deeper understanding of tumor-immune interactions and the development of immunological checkpoint inhibitors [5, 6]. Immune checkpoints are defined as various inhibitory pathways mediating self-tolerance and immune responses to limit collateral tissue damage [7]. These pathways can be utilized by tumor cells to escape detection and elimination by the immune system [8]

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