Construction and Validation of a Ferroptosis-Related lncRNA Signature as a Novel Biomarker for Prognosis, Immunotherapy and Targeted Therapy in Hepatocellular Carcinoma

作者：Ze Zhang, Wenwen Zhang, Yafei Wang, Tao Wan, Bingyang Hu, Chonghui Li, Xinlan Ge, Shichun Lu · 发表于：Frontiers in Cell and Developmental Biology · 年份：2022 · DOI：10.3389/fcell.2022.792676 · 被引用次数：52 · 研究领域：Cancer-related molecular mechanisms research、RNA modifications and cancer、Ferroptosis and cancer prognosis

Recently, immunotherapy combined with targeted therapy has significantly prolonged the survival time and improved the quality of life of patients with hepatocellular carcinoma (HCC). However, HCC treatment remains challenging due to the high heterogeneity of this malignancy. Sorafenib, the first-line drug for the treatment of HCC, can inhibit the progression of HCC by inducing ferroptosis. Ferroptosis is associated with the formation of an immunosuppressive microenvironment in tumours. Moreover, long non-coding RNAs (lncRNAs) are strongly associated with ferroptosis and the progression of HCC. Discovery of ferroptosis-related lncRNAs (FR-lncRNAs) is critical for predicting prognosis and the effectiveness of immunotherapy and targeted therapies to improve the quality and duration of survival of HCC patients. Herein, all cases from The Cancer Genome Atlas (TCGA) database were divided into training and testing groups at a 6:4 ratio to construct and validate the lncRNA signatures. Least Absolute Shrinkage and Selection Operator (LASSO) regression and Cox regression analyses were used to screen the six FR-lncRNAs (including MKLN1-AS, LINC01224, LNCSRLR, LINC01063, PRRT3-AS1, and POLH-AS1). Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curve analyses demonstrated the optimal predictive prognostic ability of the signature. Furthermore, a nomogram indicated favourable discrimination and consistency. For further validation, we used real-time quantitative polymerase ch...