Cellular senescence‐related long noncoding ribonucleic acids: Predicting prognosis in hepatocellular carcinoma

Abstract

Abstract Background Due to their inherent role in cell function, long non‐coding ribonucleic acids (lncRNAs) mediate changes in the microenvironment, and thereby participate in the development of cellular senescence. Aims This study aimed to identify cellular senescence‐related lncRNAs that could predict the prognosis of liver cancer. Methods and Results Gene expression and clinical data were downloaded from the UCSC Xena platform, ICGC, and TCGA databases. Cox regression and LASSO regression were used to establish a cellular senescence‐related lncRNA model. ROC curves and Kaplan–Meier survival curves were then constructed to predict patient prognosis. Cox regression analysis and clinical characteristics were used to evaluate the capability of the model. Tumor mutational burden and tumor‐infiltrating immune cell analyses were subsequently performed in the risk subgroups and the samples in the entire cohort were reclustered. Finally, potential small molecule immune‐targeted drugs were identified based on the model. The cellular senescence‐related prognostic model that was constructed based on AGAP11 and FAM182B. Along with the results of Cox regression and Lasso regression, the risk score was found to be an independent factor for predicting overall survival in cohorts. In the subgroup analysis, the prognosis of the low‐risk group in each cohort was significantly higher than that of the high‐risk group; the area under temporal ROC curves and clinical ROC curves were all greater than 0.65, respectively. C‐index shows that the risk scores are greater than 0.6, showing the stability of the model. The high‐risk group demonstrated lower tumor microenvironment and higher tumor mutational burden scores, further verifying the reliability of the model grouping results. Analysis of tumor‐infiltrating immune cells indicated that CD8+ and γδ T cells were more abundant among patients in the low‐risk group; cluster reorganization indicated that the two groups had different prognoses and proportions of immune cells. The p value of potential drugs predicted based on the expression of model lncRNAs were all less than .05, demonstrating the potential of model lncRNAs as therapeutic targets to some extent. Conclusion A prognostic model based on cellular senescence‐associated lncRNAs was established and this may be used as a potential biomarker for the prognosis assessment of liver cancer patients.

Keywords

• cellular senescence
• hepatocellular carcinoma
• long noncoding ribonucleic acids
• prognostic model