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.
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