Construction and verification of a novel circadian clock related long non-coding RNA model and prediction of treatment for survival prognosis in patients with hepatocellular carcinoma

Abstract

Abstract Circadian clock genes are significant in the occurrence and development of HCC and long-non coding RNAs (lncRNAs) are closely related to HCC progression. In this study, we aimed to establish a prognostic risk model for HCC. Circadian clock-related lncRNAs expressed in HCC were extracted from The Cancer Genome Atlas. A nomogram was established to predict individual survival rate. Biological processes enriched for risk model transcripts were investigated by Gene Set Enrichment Analysis. Further, we evaluated the relationship between risk score and immune-checkpoint inhibitor-related gene expression level. The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to assess the sensitivity of tumors in high- and low-risk score groups to different drugs. A total of 11 circadian clock-related lncRNAs were included in multi-Cox proportional hazards model analysis to establish a risk model. Univariate and multivariate Cox regression analysis showed that the risk model was an independent risk factor in HCC. The risk model was a significantly associated with the immune signature. Further GDSC analysis indicated that patients in each risk score group may be sensitive to different anti-cancer drugs. QRT-PCR analysis results showed that C012073.1, PRRT3-AS1, TMCC1-AS1, LINC01138, MKLN1-AS, KDM4A-AS1, AL031985.3, POLH-AS1, LINC01224, and AC099850.3 were more highly expressed in Huh-7 and HepG2, compared to LO2, while AC008549.1 were lower expressed. Our work established a prognostic model for HCC. Risk score analysis indicated that the model is significantly associated with modulation tumor immunity and could be used to guide more effective therapeutic strategies in the future.

Keywords

• Hepatocellular carcinoma
• Circadian clock
• lncRNA
• Immune infiltration
• Risk model