AUTHOR=Li Jia , Zhang Yinbin , Li Chaofan , Wu Huizi , Feng Cong , Wang Weiwei , Liu Xuan , Zhang Yu , Cai Yifan , Jia Yiwei , Qiao Hao , Wu Fei , Zhang Shuqun TITLE=A lactate-related LncRNA model for predicting prognosis, immune landscape and therapeutic response in breast cancer JOURNAL=Frontiers in Genetics VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.956246 DOI=10.3389/fgene.2022.956246 ISSN=1664-8021 ABSTRACT=

Breast cancer (BC) has the highest incidence rate of all cancers globally, with high heterogeneity. Increasing evidence shows that lactate and long non-coding RNA (lncRNA) play a critical role in tumor occurrence, maintenance, therapeutic response, and immune microenvironment. We aimed to construct a lactate-related lncRNAs prognostic signature (LRLPS) for BC patients to predict prognosis, tumor microenvironment, and treatment responses. The BC data download from the Cancer Genome Atlas (TCGA) database was the entire cohort, and it was randomly assigned to the training and test cohorts at a 1:1 ratio. Difference analysis and Pearson correlation analysis identified 196 differentially expressed lactate-related lncRNAs (LRLs). The univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were used to construct the LRLPS, which consisted of 7 LRLs. Patients could be assigned into high-risk and low-risk groups based on the medium-risk sore in the training cohort. Then, we performed the Kaplan–Meier survival analysis, time-dependent receiver operating characteristic (ROC) curves, and univariate and multivariate analyses. The results indicated that the prognosis prediction ability of the LRLPS was excellent, robust, and independent. Furthermore, a nomogram was constructed based on the LRLPS risk score and clinical factors to predict the 3-, 5-, and 10-year survival probability. The GO/KEGG and GSEA indicated that immune-related pathways differed between the two-risk group. CIBERSORT, ESTIMATE, Tumor Immune Dysfunction and Exclusion (TIDE), and Immunophenoscore (IPS) showed that low-risk patients had higher levels of immune infiltration and better immunotherapeutic response. The pRRophetic and CellMiner databases indicated that many common chemotherapeutic drugs were more effective for low-risk patients. In conclusion, we developed a novel LRLPS for BC that could predict the prognosis, immune landscape, and treatment response.