Abstract
BackgroundEarly recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are deeply involved in HCC prognosis. In this study, we aimed to establish a prognostic lncRNA signature for HCC early recurrence.MethodsThe lncRNA expression profile and corresponding clinical data were retrieved from total 299 HCC patients in TCGA database. LncRNA candidates correlated to early recurrence were selected by differentially expressed gene (DEG), univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. A 25-lncRNA prognostic signature was constructed according to receiver operating characteristic curve (ROC). Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the performance of this signature. ROC and nomogram were used to evaluate the integrated models based on this signature with other independent clinical risk factors. Gene set enrichment analysis (GSEA) was used to reveal enriched gene sets in the high-risk group. Tumor infiltrating lymphocytes (TILs) levels were analyzed with single sample Gene Set Enrichment Analysis (ssGSEA). Immune therapy response prediction was performed with TIDE and SubMap. Chemotherapeutic response prediction was conducted by using Genomics of Drug Sensitivity in Cancer (GDSC) pharmacogenomics database.ResultsCompared to low-risk group, patients in high-risk group showed reduced disease-free survival (DFS) in the training (p < 0.0001) and validation cohort (p = 0.0132). The 25-lncRNA signature, AFP, TNM and vascular invasion could serve as independent risk factors for HCC early recurrence. Among them, the 25-lncRNA signature had the best predictive performance, and combination of those four risk factors further improves the prognostic potential. Moreover, GSEA showed significant enrichment of “E2F TARGETS”, “G2M CHECKPOINT”, “MYC TARGETS V1” and “DNA REPAIR” pathways in the high-risk group. In addition, increased TILs were observed in the low-risk group compared to the high-risk group. The 25-lncRNA signature negatively associates with the levels of some types of antitumor immune cells. Immunotherapies and chemotherapies prediction revealed differential responses to PD-1 inhibitor and several chemotherapeutic drugs in the low- and high-risk group.ConclusionsOur study proposed a 25-lncRNA prognostic signature for predicting HCC early recurrence, which may guide postoperative treatment and recurrence surveillance in HCC patients.
Highlights
Recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC)
HCC dataset preparation and identification of candidate long non-coding RNA (lncRNA) from the training cohort HCC RNA-seq data and corresponding clinical information were downloaded from the The Cancer Genome Atlas (TCGA)-LIHC (Liver Hepatocellular Carcinoma) project
Univariate and multivariate Cox regression analyses showed that the 25-lncRNA risk score, serum AFP, TNM stage and vascular invasion (VI) were independent prognostic factors for HCC early recurrence
Summary
Recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) are deeply involved in HCC prognosis. We aimed to establish a prognostic lncRNA signature for HCC early recurrence. Hepatocellular carcinoma (HCC) compromises 75–85% of primary liver cancer [1]. The main clinical curative treatments for HCC include liver transplantation, percutaneous radiofrequency ablation and liver resection, among which liver resection is the most employed treatment [2]. 5-year overall survival rate reaches up to 50%, recurrence occurs in more than 70% HCC patients after curative surgery [3]. The recurrence within 2-year after resection is defined as early recurrence, whereas the recurrence > 2-year is defined as late recurrence. HCC patients with early recurrence usually showed poorer prognosis [4]
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