Identification of a four long non-coding RNA (lncRNA) Signature for Predicting Prognosis of Patients with Non-Small Cell Lung Cancer: a Multicenter Study in China
Abstract Background:This study aims to identify a long non-coding RNA (lncRNA) signature for predicting survival in non-small-cell lung carcinoma (NSCLC) patients and providing additional prognostic information to the tumor node metastasis (TNM) staging system. Methods: NSCLC cases from a hospital were divided into a discovery cohort (n=194) and validation cohort (n=172) and analyzed using a custom lncRNA microarray. Another 73 cases obtained from another hospital were assayed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The differentially expressed lncRNAs were detected by significance analysis of microarrays (SAM) program and used for identifying those associated with survival in the discovery cohort, which were then employed to construct a prognostic lncRNA signature using a risk-score method. The signature was then confirmed in the validation and independent cohort as well. Results: The discovery cohort was found to comprise of 305 lncRNAs, which showed differential expression between the NSCLC and the corresponding normal lung tissues, a 4-lncRNA signature was identified that was found to significantly correlate with the survival of the NSCLC patients. This signature was further validated in the validation and independent cohort. Moreover, multivariate Cox analysis demonstrates that the 4-lncRNA signature is independent of the TNM staging system.as a risk-score model. The receiver operating characteristic (ROC) curve indicates that the prognostic value of the combined model is significantly higher than that of TNM staging alone in all the cohorts. Conclusions:This study identified a 4-lncRNA signature, which is a powerful prognostic biomarker which related to patient survival in addition to the traditional TNM staging system.