Identification of Key Genes Affecting the Tumor Microenvironment and Prognosis of Triple-Negative Breast Cancer.

Jiarong Yi,Xiazi Zouxu,Xinjian Huang,Jikun Feng,Wenjing Zhong,Zeyu Shuang,Siqi Li,Haoming Wu

doi:10.3389/fonc.2021.746058

Abstract

Although the tumor microenvironment (TME) plays an important role in the development of many cancers, its roles in breast cancer, especially triple-negative breast cancer (TNBC), are not well studied. This study aimed to identify genes related to the TME and prognosis of TNBC. Firstly, we identified differentially expressed genes (DEG) in the TME of TNBC, using Expression data (ESTIMATE) datasets obtained from the Cancer Genome Atlas (TCGA) and Estimation of Stromal and Immune cells in Malignant Tumor tissues. Next, survival analysis was performed to analyze the relationship between TME and prognosis of TNBC, as well as determine DEGs. Genes showing significant differences were scored as alternative genes. A protein-protein interaction (PPI) network was constructed and functional enrichment analysis conducted using the DEG. Proteins with a degree greater than 5 and 10 in the PPI network correspond with hub genes and key genes, respectively. Finally, CCR2 and CCR5 were identified as key genes in TME and prognosis of TNBC. Finally, these results were verified using Gene Expression Omnibus (GEO) datasets and immunohistochemistry of TNBC patients. In conclusion, CCR2 and CCR5 are key genes in the TME and prognosis of TNBC with the potential of prognostic biomarkers in TNBC.

Highlights

Breast cancer is the second leading cause of cancer related deaths among women worldwide, with a prevalence of 11.7% and a mortality rate of 6.9% [1]
The present study aimed to identify key genes associated with Triple negative breast cancer (TNBC) microenvironment and prognosis of patients
Triple negative breast cancer (TNBC) datasets were obtained from the the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases

Summary

Introduction

Breast cancer is the second leading cause of cancer related deaths among women worldwide, with a prevalence of 11.7% and a mortality rate of 6.9% [1]. In 2017 alone, it was estimated that 30% of all new cancer cases [252,710], among women in America, were breast cancer [3]. Based on the characteristics of molecular markers, breast cancer is divided into 3 major subtypes, namely estrogen receptor positive and progesterone receptor positive (luminal A, luminal B), HER2 overexpression (HER2+) and triple negative breast cancer (TNBC). Triple negative breast cancer (TNBC) is the subtype of breast cancer that tests negative for estrogen receptors (ER), progesterone receptors (PR), and excess HER2. TNBC accounts for about 15% of the total breast

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