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

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.

A novel disulfidptosis-related lncRNA signature for predicting prognosis and potential targeted therapy in hepatocellular carcinoma

“…[32] In addition, Zhang et al identified MKLN1-AS as an important component of HCC prognostic models. [33] All these findings, which are in line with the results of our bioinformatics analyses, indicate that MKLN1-AS could serve as a potential marker for diagnosis and prognosis, as well as a therapeutic target in HCC patients. The Wei et.al find that the inhibition of lncRNA AL590705.3 expression decreased the proliferative capacity of HCC cells but enhanced FDX1 expression.…”

Crosstalk among disulfidptosis-related lncRNAs in lung adenocarcinoma reveals a correlation with immune profile and clinical prognosis

“…The reduced levels of lncRNA LINC00987 in LUAD predict poor prognosis and decreased immunotherapy response [ 32 ]. Emerging evidence has suggested that POLH-AS1 can be used as a prognostic and survival marker in patients with hepatocellular carcinoma [ 33 , 34 ]. SVIL-AS1 suppressed chemoresistance by sponging miR-103a while increasing the levels of ICE1, and it could be the possible anti-LUAD chemotherapeutic target [ 35 ].…”

Identification of an immune-related 6-lncRNA panel with a good performance for prognostic prediction in hepatocellular carcinoma by integrated bioinformatics analysis

“…LINC01224 has been proved by multiple bioinformatics studies to have great potential as a biomarker of HCC prognosis and immune response and is related to pyroptosis and ferroptosis. [62][63][64][65][66][67] CTD-2510F5.4 was identified as a potential prognostic biomarker in the bioinformatics study of lung adenocarcinoma, gastric cancer, and HCC and is related to ferroptosis in HCC. [67][68][69][70][71][72] RP1-228H13.5 has been revealed to be related to necroptosis, autophagy, pyroptosis, ferroptosis, glycolysis, and other mechanisms of HCC, and has been identified as a prognostic marker of HCC by many studies.…”

“…Overexpression Related to pyroptosis and ferroptosis [62][63][64][65][66][67] CTD-2510F5. 4 Overexpression Related to ferroptosis [67][68][69][70][71][72] RP1-228H13.…”