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Abstract

Objective: The present aimed to establish a prognostic signature based on autophagy-related long non-coding RNAs (lncRNAs) analysis in hepatocellular carcinoma (HCC) patients. Methods: HCC patients from The Cancer Genome Atlas (TCGA) were taken as the training cohort, and patients from International Cancer Genome Consortium (ICGC) were treated as the validation cohort. Autophagy-related lncRNAs were obtained via co-expression network analysis. According to univariate and multivariate analyses, a multigene prognostic signature was constructed in the training cohort. The predictive power of the signature was confirmed in both cohorts. The detail functions were investigated using functional analysis. The single-sample gene-set enrichment analysis (ssGSEA) score was used to evaluate the tumor microenvironment. The expression levels of immunotherapy and targeted therapy targets were compared between the two risk groups. Finally, a nomogram was constructed by integrating clinicopathological parameters with independently predictive value and the risk score. Results: Four autophagy-related lncRNAs were identified to establish a prognostic signature, which separated patients into high- and low-risk groups. Survival analysis showed patients in the high-risk group had a shorter survival time in both cohorts. A time-independent receiver-operating characteristic (ROC) curve and principal component analysis (PCA) confirmed that the prognostic signature had a robust predictive power and reliability in both cohorts. Functional analysis indicated the expressed genes in the high-risk group mainly enriched in autophagy- and cancer-related pathways. ssGSEA revealed that the different risk groups were associated with the tumor microenvironment. Moreover, the different risk groups had positive correlations with the expressions of specific mutant genes. Multivariate analysis showed that the risk score also exhibited excellent predictive power irrespective of clinicopathological characteristics in both cohorts. A nomogram was established. The nomogram showed good discrimination, with a C-index of 0.739 and good calibration Conclusion: The four autophagy-related lncRNAs could be used as biological biomarkers and therapeutic targets. The prognostic signature and nomogram might aid clinicians in individual treatment optimization and clinical decision-making for HCC patients.