Peer Review #3 of "development and Validation of Ferroptosis-Related Lncrnas Signature for Hepatocellular Carcinoma (V0.1)"

Background.Hepatocellular carcinoma (HCC) with high heterogeneity is one of the most frequent malignant tumors throughout the world.However, there is no research to establish ferroptosis-related lncRNAs (FRlncRNAs) signature for the patients with HCC.Therefore, this study was designed to establish a novel FRlncRNAs signatures to preferable predict the survival of patients with HCC.Method.The expression profiles of lncRNAs were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database.FRlncRNAs co-expressed with ferroptosis-related gene were utilized to establish signature.Cox regression was used to construct a novel three FRlncRNAs signature in TCGA cohort, which was verified in GEO validation cohort.Results.Three differently expressed FRlncRNAs significantly associated with prognosis of HCC were identified, which composed a novel FRlncRNAs signature.According to the FRlncRNAs signature, the patients with HCC could be divided into low-and high-risk groups.Patients with HCC in high-risk group displayed shorter overall survival (OS) contrasted with those in low-risk group (P < 0.001 in TCGA cohort and P = 0.045 in GEO cohort).This signature could serve as a significantly independent predictor in Cox regression (multivariate HR > 1, P < 0.001), which was verified to a certain extent in GEO cohort (univariate HR > 1, P < 0.05).Meanwhile, it was also a useful tool in predicting survival among each stratum of gender, age, grade, stage, and etiology,etc.This signature was connected with immune cell infiltration (i.e., Macrophage, Myeloid dendritic cell, and Neutrophil cell, etc.) and immune checkpoint blockade targets (PD-1, CTLA-4, and TIM-3). Conclusion.The three FRlncRNAs might be potential therapeutic targets for patients, and their signature could be utilized for prognostic prediction in HCC.