期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 234, 期 9, 页码 16021-16031出版社
WILEY
DOI: 10.1002/jcp.28260
关键词
long noncoding RNA; lung adenocarcinoma; mutation; prognosis; TP53
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=9.97x10 (-8) and 1.41x10 (-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=1.00x10 (-6) and 7.27x10 (-4), respectively). The LPS also significantly divided survival in clinically important subsets, including Stage I (p=9.00x10 (-4) and 4.40x10 (-2), respectively), KRAS wild-type (WT), KRAS mutant (p=4.00x10 (-3) and 4.30x10 (-2), respectively) and EGFR WT (p=2.00x10 (-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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