A mitochondrial function-related LncRNA signature predicts prognosis and immune microenvironment for breast cancer

Abstract

Mitochondrial function, as the core of the cell's energy metabolism, is firmly connected to cancer metabolism and growth. However, the involvement of long noncoding RNAs (lncRNAs) related to mitochondrial function in breast cancer (BRCA) has not been thoroughly investigated. As a result, the objective of this research was to dissect the prognostic implication of mitochondrial function-related lncRNAs and their link to the immunological microenvironment in BRCA. The Cancer Genome Atlas (TCGA) database was used to acquire clinicopathological and transcriptome information for BRCA samples. Mitochondrial function-related lncRNAs were recognized by coexpression analysis of 944 mitochondrial function-related mRNAs obtained from the MitoMiner 4.0 database. A novel prognostic signature was built in the training cohort using integrated analysis of mitochondrial function-related lncRNA and the corresponding clinical information through univariate analysis, lasso regression, and stepwise multivariate Cox regression analysis. The prognostic worth was judged in the training cohort and validated in the test cohort. In addition, functional enrichment and immune microenvironment analyses were performed to explore the risk score on the basis of the prognostic signature. An 8-mitochondrial function-related lncRNA signature was generated by integrated analysis. Individuals within the higher-risk category had a worse overall survival rate (OS) (training cohort: P < 0.001; validation cohort: P < 0.001; whole cohort: P < 0.001). The risk score was identified as an independent risk factor by multivariate Cox regression analysis (training cohort: HR 1.441, 95% CI 1.229–1.689, P < 0.001; validation cohort: HR 1.343, 95% CI 1.166–1.548, P < 0.001; whole cohort: HR 1.241, 95% CI 1.156–1.333, P < 0.001). Following that, the predictive accuracy of the model was confirmed by the ROC curves. In addition, nomograms were generated, and the calibration curves revealed that the model had excellent prediction accuracy for 3- and 5-year OS. Besides, the higher-risk BRCA individuals have relatively decreased amounts of infiltration of tumor-killing immune cells, lower levels of immune checkpoint molecules, and immune function. We constructed and verified a novel mitochondrial function-related lncRNA signature that might accurately predict the outcome of BRCA, play an essential role in immunotherapy, and might be exploited as a therapeutic target for precise BRCA therapy.