As the fifth most common cancer worldwide, Hepatocellular carcinoma (HCC) is also the third most common cause of cancer-related death in China. Several lncRNAs have been demonstrated to be associated with occurrence and prognosis of HCC. However, identification of prognostic lncRNA signature for HCC with expression profiling data has not been conducted yet.
With the reuse of public available TCGA data, expression profiles of lncRNA for 371 patients with HCC were obtained and analyzed to find the independent prognostic lncRNA. Based on the expression of lncRNA, researchers from the Hospital of Sichuan University developed a risk score model, which was evaluated by survival analysis and ROC (receiver operating characteristic) curve. Enrichment analysis was performed to predict the possible role of the identified lncRNA in HCC prognosis.
Four lncRNAs (RP11-322E11.5, RP11-150O12.3, AC093609.1, CTC-297N7.9) were found to be significantly and independently associated with survival of HCC patients. The researchers used these four lncRNAs to construct a risk score model, which exhibited a strong ability to distinguish patients with significantly different prognosis (HR = 2.718, 95% CI [2.103-3.514], p = 2.32e-14). Similar results were observed in the subsequent stratification survival analysis for HBV infection status and pathological stage. The ROC curve also implied our risk score as a good indicator for 5-year survival prediction. Furthermore, enrichment analysis revealed that the four signature lncRNAs may be involved in multiple pathways related to tumorigenesis and prognosis.
Identification of prognostic lncRNA for patients with HCC
(A) Heatmap of 1,074 differentially expressed lncRNAs between normal and tumor tissues. (B) Z score of 1,074 deregulated lncRNAs from univariate Cox aggression analysis (brown dots indicate lncRNAs with p value <0.01). (C) Z score of four identified prognostic lncRNAs from univariate and multivariate Cox aggression analysis.
This study recognized four lncRNAs to be significantly associated with prognosis of liver cancer, and could provide novel insights into the potential mechanisms of HCC progression. Additionally, CTC-297N7.9 may influence the downstream TMEM220 gene expression through cis-regualtion. Nevertheless, further well-designed experimental studies are needed to validate these findings.