Immune Cell Infiltration and Relevant Gene Signatures in the Tumor Microenvironment that Significantly Associates With the Prognosis of Patients With Breast Cancer.

Qiang Xu,Songnan Zhang,Honghua Sun,Yongmin Jin,Xinghe Yan,Xiuying Jin,Junhua Liang,Zhezhu Han

doi:10.3389/fmolb.2022.823911

Qiang Xu, Songnan Zhang + Show 6 more

Open Access

https://doi.org/10.3389/fmolb.2022.823911

Copy DOI

Abstract

Breast cancer is the most common malignancy and the leading cause of cancer-related deaths in women. Recent studies have investigated the prognostic value of the tumor microenvironment (TME)-related genes in breast cancer. The purpose of this research is to identify the immune-associated prognostic signature for breast cancer evaluate the probability of their prognostic value and compare the current staging system. In this study, we comprehensively evaluated the infiltration patterns of TME in 1,077 breast cancer patients downloaded from TCGA by applying the ssGSEA method to the transcriptome of these patients. Thus, generated two groups of immune cell infiltration. Based on two groups of low infiltration and high infiltration immune cell groups, 983 common differentially expressed genes were found using the limma algorithm. In addition, studying potential mechanisms, the GSEA method was used to indicate some pathways with remarkable enrichment in two clusters of immune cell infiltration. Finally, the seven immune-associated hub genes with survival as prognostic signatures were identified by using univariate Cox, survival, and LASSO analyses and constructed a TME score. The prognostic value of the TME score was self-validated in the TCGA cohort and further validated in an external independent set from METABRIC and GEO database by time-dependent survival receiver operation. Univariate and multivariate analyses of clinicopathological characteristics indicated that the TME score was an independent prognostic factor. In conclusion, the proposed TME score model should be considered as a prognostic factor, similar to the current TNM stage, and the seven immune-related genes can be a valuable potential biomarker for breast cancer.

Highlights

Breast cancer is one of the major malignancies among females, and mortality remains the second main cause of cancer-related deaths worldwide (Siegel et al, 2019)
The high heterogeneity of breast cancer exists in the molecular level of tumor cells, as well as in the tumor microenvironment (TME) (Baker et al, 2018)
We identified and validated the prognosis value of seven immune-associated genes with the survival of breast cancer datasets obtained from The Cancer Genome Atlas (TCGA)

Summary

Introduction

Breast cancer is one of the major malignancies among females, and mortality remains the second main cause of cancer-related deaths worldwide (Siegel et al, 2019). Tumor Microenvironment in Breast Cancer used in clinical practice to guide treatment decisions and predict the prognosis of breast cancer patients. Increasing attention has been paid to the research on the tumor microenvironment (TME) for its tremendous potential development capacity in the prognosis of patients with breast cancer (Baxevanis et al, 2021). Successful elimination of tumors through immunotherapy requires activating the immune system. The depletion or short-lived activation of immune cells and inhibition of microenvironment formation leads to resistance to immunotherapy (Tang et al, 2016). Immuneassociated genes and infiltration of immune cells in TME play a vital role in the properties of tumors, such as proliferation and development (Gonzalez et al, 2018). Characterizing the immune-associated genes with overall survival may present a prospective reference for breast cancer therapy and prognosis

Objectives

Methods

Findings

Conclusion