AUTHOR=Dai Yin-wei , Wen Zhi-kai , Wu Zhi-xuan , Wu Hao-dong , Lv Lin-xi , Yan Cong-zhi , Liu Cong-hui , Wang Zi-qiong , Zheng Chen 

TITLE=Amino Acid Metabolism-Related lncRNA Signature Predicts the Prognosis of Breast Cancer

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.880387

DOI=10.3389/fgene.2022.880387

ISSN=1664-8021

ABSTRACT=<p><bold>Background and Purpose:</bold> Breast cancer (BRCA) is the most frequent female malignancy and is potentially life threatening. The amino acid metabolism (AAM) has been shown to be strongly associated with the development and progression of human malignancies. In turn, long noncoding RNAs (lncRNAs) exert an important influence on the regulation of metabolism. Therefore, we attempted to build an AAM-related lncRNA prognostic model for BRCA and illustrate its immune characteristics and molecular mechanism.</p><p><bold>Experimental Design:</bold> The RNA-seq data for BRCA from the TCGA-BRCA datasets were stochastically split into training and validation cohorts at a 3:1 ratio, to construct and validate the model, respectively. The amino acid metabolism-related genes were obtained from the Molecular Signature Database. A univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) regression, and a multivariate Cox analysis were applied to create a predictive risk signature. Subsequently, the immune and molecular characteristics and the benefits of chemotherapeutic drugs in the high-risk and low-risk subgroups were examined.</p><p><bold>Results:</bold> The prognostic model was developed based on the lncRNA group including LIPE-AS1, AC124067.4, LINC01655, AP005131.3, AC015802.3, USP30-AS1, SNHG26, and AL589765.4. Low-risk patients had a more favorable overall survival than did high-risk patients, in accordance with the results obtained for the validation cohort and the complete TCGA cohort. The elaborate results illustrated that a low-risk index was correlated with DNA-repair–associated pathways; a low <italic>TP53</italic> and <italic>PIK3CA</italic> mutation rate; high infiltration of CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells, and M1 macrophages; active immunity; and less-aggressive phenotypes. In contrast, a high-risk index was correlated with cancer and metastasis-related pathways; a high <italic>PIK3CA</italic> and <italic>TP53</italic> mutation rate; high infiltration of M0 macrophages, fibroblasts, and M2 macrophages; inhibition of the immune response; and more invasive phenotypes.</p><p><bold>Conclusion:</bold> In conclusion, we attempted to shed light on the importance of AAM-associated lncRNAs in BRCA. The prognostic model built here might be acknowledged as an indispensable reference for predicting the outcome of patients with BRCA and help identify immune and molecular characteristics.</p>