Identification of Five Immune-Related lncRNAs Predicting Survival and Tumor Microenvironment Characteristics in Breast Cancer.

Ran Xiao,Yuanyuan Tan,Meng Yang,Duolu Li,Rumeng Ding,Prem Chapagain

doi:10.1155/2021/6676692

Abstract

A common cancer in females, breast cancer (BRCA) mortality has been recently reduced; however, the prognosis of BRCA patients remains poor. This study attempted to develop prognostic immune-related long noncoding RNAs (lncRNAs) for BRCA and identify the effects of these lncRNAs on the tumor microenvironment (TME). Gene expression data from The Cancer Genome Atlas (TCGA) database were collected in order to select differentially expressed lncRNAs. Immune-related lncRNAs were downloaded from the ImmLnc database, where 316 immune-related lncRNAs were identified, 12 of which were found to be significantly related to the prognosis of BRCA patients. Multivariate cox regression analysis was then applied to construct prognostic immune-related lncRNAs as the risk model, including C6orf99, LINC00987, SIAH2-AS1, LINC01010, and ELOVL2-AS1. High-risk and low-risk groups were distinguished according to the median of immune-related risk scores. Accordingly, the overall survival (OS) in the high-risk group was observed to be shorter than that in the low-risk group. qRT-PCR analysis demonstrated that lncRNA expression levels in BRCA cell lines were in basic agreement with predictions except for LINC00987. By validating numerous clinical samples, lncRNA C6orf99 was shown to be highly expressed in the advanced stage, while LINC01010 and SIAH2-AS1 decreased in the advanced T-stage and M-stage. Moreover, the expression of LINC0098 was found to be significantly decreased among the groups (>50 years old). Gene set enrichment analysis (GSEA) was applied to analyze the cancer hallmarks and immunological characteristics of the high-risk and low-risk groups. Importantly, the TIMER database demonstrated that this immune-related lncRNA risk model for breast cancer is related to the infiltration of immune cells. In conclusion, the results indicated that five immune-related lncRNAs could be used as a prognostic model and may even accelerate immunotherapy for BRCA patients.

Highlights

Breast cancer (BRCA), one of the most common cancers among women in the world, is the main cause of death in females whose incidence increases every year [1, 2]
The RNA-seq of 1039 BRCA patients and 113 normal samples was collected from The Cancer Genome Atlas (TCGA)
The RNA-seq data of long noncoding RNAs (lncRNAs) and mRNA were separated, and the gene read counts were normalized to the trimmed mean of M values (TMM) by

Summary

Introduction

Breast cancer (BRCA), one of the most common cancers among women in the world, is the main cause of death in females whose incidence increases every year [1, 2]. Certain studies have recently reported that the prognosis of BRCA patients is related to immunity [4, 5]. It is necessary to ascertain novel immune predictors in order to improve the diagnosis and treatment of BRCA. The tumor microenvironment (TME), which is composed of immune cells, mesenchymal cells, cytokines, and other molecules, is involved in the occurrence, development, and prognosis of tumors [6, 7]. Various key genetic markers can change the prognosis of BRCA patients in TME [8, 9]. Tumor-infiltrating lymphocytes (TILs) of TME are key in tumor immunotherapy [10]. Recent studies have demonstrated that TILs can act as a clinicopathologic prognostic model for BRCA patients [11, 12], and increasing

Methods

Results

Conclusion