Abstract
BackgroundPrognostic assessment is imperative for clinical management of patients with hepatocellular carcinoma (HCC). Most reported prognostic signatures are based on risk scores summarized from quantitative expression level of candidate genes, which are vulnerable against experimental batch effects and impractical for clinical application. We aimed to develop a robust qualitative signature to assess individual survival risk for HCC patients.MethodsLong non-coding RNA (lncRNA) pairs correlated with overall survival (OS) were identified and an optimal combination of lncRNA pairs based on the majority voting rule was selected as a classification signature to predict the overall survival risk in the cancer genome atlas (TCGA). Then, the signature was further validated in two external datasets. Besides, biomolecular characteristics, immune infiltration status, and chemotherapeutics efficacy of different risk groups were further compared. Finally, we performed key lncRNA screening and validated it in vitro.ResultsA signature consisting of 50 lncRNA pairs (50-LPS) was identified in TCGA and successfully validated in external datasets. Patients in the high-risk group, when at least 25 of the 50-LPS voted for high risk, had significantly worse OS than the low-risk group. Multivariate Cox, receiver operating characteristic (ROC) curve and decision curve analyses (DCA) demonstrated that the 50-LPS was an independent prognostic factor and more powerful than other available clinical factors in OS prediction. Comparison analyses indicated that different risk groups had distinct biomolecular characteristics, immune infiltration status, and chemotherapeutics efficacy. TDRKH-AS1 was confirmed as a key lncRNA and associated with cell growth of HCC.ConclusionsThe 50-LPS could not only predict the prognosis of HCC patients robustly and individually, but also provide theoretical basis for therapy. Besides, TDRKH-AS1 was identified as a key lncRNA in the proliferation of HCC. The 50-LPS might guide personalized therapy for HCC patients in clinical practice.
Highlights
Prognostic assessment is imperative for clinical management of patients with hepatocellular carcinoma (HCC)
Among the 55 Long non-coding RNA (lncRNA) included in the 50 lncRNA pairs (50-LPS), TDRKH-AS1 was confirmed as a key lncRNA and associated with cell growth of HCC
By setting a cut-off less than 0.05 of false discovery rate (FDR) in the univariate Cox proportional hazards regression model, we identified 119 overall survival (OS)-associated lncRNAs
Summary
Prognostic assessment is imperative for clinical management of patients with hepatocellular carcinoma (HCC). We aimed to develop a robust qualitative signature to assess individual survival risk for HCC patients. It is of critical importance to predict the prognosis of HCC patients after surgery for guiding clinical therapy and patient management. Used clinical features and biomarkers, such as TNM staging system, BCLC staging system, and serum alpha-fetoprotein (AFP) level, were insufficient in providing accurate prognostic evaluation for HCC patients in clinical practice [4, 5]. The most widely used serum AFP level was reported to be nearly half-negative in early and small size HCC patients [6], which crippled the prognostic ability of serum AFP. The TNM and BCLC staging system were not widely used for the differences in etiology and genetic background of HCC patients [4]
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