A novel LncRNA‐based prognostic score reveals TP53‐dependent subtype of lung adenocarcinoma with poor survival. Issue 9 (10th February 2019)

• Record Type: Journal Article
• Authors: Kumar, Pranjal; Khadirnaikar, Seema; Shukla, Sudhanshu Kumar
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 9(2019:Sep.)
• Page Start: 16021
• Page End: 16031
• Publication Date: 2019-02-10
• Subjects: long noncoding RNA -- lung adenocarcinoma -- mutation -- prognosis -- TP53; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28260
• Languages: English
• ISSNs: 0021-9541

Abstract

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. Abstract : A novel risk score based on the expression of four long noncoding RNAs can predict the survival of lung adenocarcinoma patients. Patients with poor survival showed a strong correlation with TP53 mutations.