A novel LncRNA-based prognostic score reveals TP53-dependent subtype of lung adenocarcinoma with poor survival

J Cell Physiol. 2019 Sep;234(9):16021-16031. doi: 10.1002/jcp.28260. Epub 2019 Feb 10.

Abstract

The prognostic signatures play an essential role in the era of personalised therapy for cancer patients including lung adenocarcinoma (LUAD). Long noncoding RNA (LncRNA), a relatively novel class of RNA, has shown to play a crucial role in all the areas of cancer biology. Here, we developed and validated a robust LncRNA-based prognostic signature for LUAD patients using three different cohorts. In the discovery cohort, four LncRNAs were identified with 10% false discovery rate and a hazard ratio of >10 using univariate Cox regression analysis. A risk score, generated from the four LncRNAs' expression, was found to be a significant predictor of survival in the discovery and validation cohort (p = 9.97 × 10 -8 and 1.41 × 10 -3 , respectively). Further optimisation of four LncRNAs signature in the validation cohort, generated a three LncRNAs prognostic score (LPS), which was found to be an independent predictor of survival in both the cohorts ( p = 1.00 × 10 -6 and 7.27 × 10 -4 , respectively). The LPS also significantly divided survival in clinically important subsets, including Stage I ( p = 9.00 × 10 -4 and 4.40 × 10 -2 , respectively), KRAS wild-type (WT), KRAS mutant ( p = 4.00 × 10 -3 and 4.30 × 10 -2 , respectively) and EGFR WT ( p = 2.00 × 10 -4 ). In multivariate analysis LPS outperformed, eight previous prognosticators. Further, individual members of LPS showed a significant correlation with survival in microarray data sets. Mutation analysis showed that high-LPS patients have a higher mutation rate and inactivation of the TP53 pathway. In summary, we identified and validated a novel LncRNA signature LPS for LUAD.

Keywords: TP53; long noncoding RNA; lung adenocarcinoma; mutation; prognosis.