A Signature of Autophagy-Related Long Non-coding RNA to Predict the Prognosis of Breast Cancer
Authors: Li Xiaoping , Chen Jishang , Yu Qihe , Huang Hui , Liu Zhuangsheng , Wang Chengxing , He Yaoming , Zhang Xin , Li Weiwen , Li Chao , Zhao Jinglin , Long Wansheng 
Published: March 2021

Background: A surge in newly diagnosed breast cancer has overwhelmed the public health system worldwide. Joint effort had beed made to discover the genetic mechanism of these disease globally. Accumulated research has revealed autophagy may act as a vital part in the pathogenesis of breast cancer.

Objective: Aim to construct a prognostic model based on autophagy-related lncRNAs and investigate their potential mechanisms in breast cancer.

Methods: The transcriptome data and clinical information of patients with breast cancer were obtained from The Cancer Genome Atlas (TCGA) database. Autophagy-related genes were obtained from the Human Autophagy Database (HADb). Long non-coding RNAs (lncRNAs) related to autophagy were acquired through the Pearson correlation analysis. Univariate Cox regression analysis as well as the least absolute shrinkage and selection operator (LASSO) regression analysis were used to identify autophagy-related lncRNAs with prognostic value. We constructed a risk scoring model to assess the prognostic significance of the autophagy-related lncRNAs signatures. The nomogram was then established based on the risk score and clinical indicators. Through the calibration curve, the concordance index (C-index) and receiver operating characteristic (ROC) curve analysis were evaluated to obtain the model's predictive performance. Subgroup analysis was performed to evaluate the differential ability of the model. Subsequently, gene set enrichment analysis was conducted to investigate the potential functions of these lncRNAs.

Results: We attained 1,164 breast cancer samples from the TCGA database and 231 autophagy-related genes from the HAD database. Through correlation analysis, 179 autophagy-related lncRNAs were finally identified. Univariate Cox regression analysis and LASSO regression analysis further screened 18 prognosis-associated lncRNAs. The risk scoring model was constructed to divide patients into high-risk and low-risk groups. It was found that the low-risk group had better overall survival (OS) than those of the high-risk group. Then, the nomogram model including age, tumor stage, TNM stage and risk score was established. The evaluation index (C-index: 0.78, 3-year OS AUC: 0.813 and 5-year OS AUC: 0.785) showed that the nomogram had excellent predictive power. Subgroup analysis showed there were difference in OS between high-risk and low-risk patients in different subgroups (stage I-II, ER positive, Her-2 negative and non-TNBC subgroups; all P &lt; 0.05). According to the results of gene set enrichment analysis, these lncRNAs were involved in the regulation of multicellular organismal macromolecule metabolic process in multicellular organisms, nucleotide excision repair, oxidative phosphorylation, and TGF-β signaling pathway.

Conclusions: We identified 18 autophagy-related lncRNAs with prognostic value in breast cancer, which may regulate tumor growth and progression in multiple ways.