Construction of risk model associated with prognosis of lung adenocarcinoma based on a set of microRNAs by analyzing TCGA database

Abstract

Objective To explore the specific prognosis related microRNAs (miRNAs) of lung adenocarcinoma (LUAD), and provide basis for prognosis prediction and individualized treatment. Methods The miRNA-Seq data and clinical information of LUAD patients were downloaded from the TCGA database, and the differentially expressed miRNAs between LUAD and adjacent normal tissues were identified by R Language. The LASSO & COX regression was used to develop a miRNA-based model for predicting patientsʹ survival in the training set (n=245) and to carry out LUAD prognostic related miRNAs screening, and to construct a linear risk model based on 7 miRNAs expression profiles. According to the risk values, the patients were divided into high and low risk groups with the median risk value as the boundary, and the effectiveness of the prognosis was verified by the risk model in the test set (n=245) and the total specimens (n=490) respectively. COX regression analysis was used to determine whether the miRNAs risk model was an independent prognostic factor. Results Seventy-two differentially expressed miRNAs were identified between LUAD and adjacent normal tissues. forty-five miRNAs were up-regulated and 27 were down-regulated in LUAD tissues. Seven survival-related miRNAs (miR-101-3p, miR-148a-3p, miR-192-5p, miR-193b-3p, miR-505-3p, miR-584-5p, and miR-99a-5p) were identified in the training set and a prognostic model based on the expression of the 7 miRNAs was developed and its coefficient was evaluated. It showed that the overall survival time of the high-risk group was significantly lower than that of the low risk group in the training set, test set and whole cohort (P<0.05). Multivariate cox regression analysis indicated that the risk model was an independent prognostic factor in the training set, test set and whole cohort (training set HR=1.97, P=0.02; test set HR=1.927, P=0.009; overall HR=1.909, P=0.001). Conclusion Seven miRNAs are identified to be significantly associated with the prognosis of LUAD patients and the risk model based on the 7 miRNAs could be an independent prognostic factor. Key words: Lung adenocarcinoma; MicroRNAs; Prognosis; TCGA