Abstract
Background Accumulating evidence proves that long noncoding RNA (lncRNA) plays a crucial role in maintaining genomic instability. However, it is significantly absent from exploring genomic instability-associated lncRNAs and discovering their clinical significance. Objective To identify crucial mutator-derived lncRNAs and construct a predictive model for prognosis and genomic instability in hepatocellular carcinoma. Methods First, we constructed a mutator hypothesis-derived calculative framework through uniting the lncRNA expression level and somatic mutation number to screen for genomic instability-associated lncRNA in hepatocellular carcinoma. We then selected mutator-derived lncRNA from the genome instability-associated lncRNA by univariate Cox analysis and Lasso regression analysis. Next, we created a prognosis model with the mutator-derived lncRNA signature. Furthermore, we verified the vital role of the model in the prognosis and genomic instability of hepatocellular carcinoma patients. Finally, we examined the potential relationship between the model and the mutation status of TP53. Results In this study, we screened 88 genome instability-associated lncRNAs and built a prognosis model with four mutator-derived lncRNAs. Moreover, the model was an independent predictor of prognosis and an accurate indicator of genomic instability in hepatocellular carcinoma. Finally, the model could catch the TP53 mutation status, and the model was a more effective indicator than the mutation status of TP53 for hepatocellular carcinoma patients. Conclusion This research adopted a reliable method to analyze the role of lncRNA in genomic instability. Besides, the prognostic model with four mutator-derived lncRNAs is an excellent new indicator of prognosis and genomic instability in hepatocellular carcinoma. In addition, this finding may help clinicians develop therapeutic systems.
Highlights
Liver cancer is one of the leading causes of cancer death in many countries, accounting for 8.2% of total cancer mortality [1]
We found that the model constructed by long noncoding RNA (lncRNA) is a stable measure to estimate the level of genomic instability and prognosis of hepatocellular carcinomas (HCCs) patients, and genomic stability had a negative relationship with prognosis in HCC
To screen genomic instability-associated lncRNAs, through sorting the patients by the cumulative number of mutations, we found that 93 patients were in the top 25%, which was the genomic instability (GI) group. 90 patients were in the bottom 25%, which was the genomic stability (GS) group
Summary
Liver cancer is one of the leading causes of cancer death in many countries, accounting for 8.2% of total cancer mortality [1]. Accumulating evidence proves that long noncoding RNA (lncRNA) plays a crucial role in maintaining genomic instability. To identify crucial mutator-derived lncRNAs and construct a predictive model for prognosis and genomic instability in hepatocellular carcinoma. We verified the vital role of the model in the prognosis and genomic instability of hepatocellular carcinoma patients. We screened 88 genome instability-associated lncRNAs and built a prognosis model with four mutator-derived lncRNAs. the model was an independent predictor of prognosis and an accurate indicator of genomic instability in hepatocellular carcinoma. The prognostic model with four mutator-derived lncRNAs is an excellent new indicator of prognosis and genomic instability in hepatocellular carcinoma. This finding may help clinicians develop therapeutic systems
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