机构:[1]Department of Medical Oncology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China内科片肿瘤内科云南省第一人民医院[2]Department of Medical Oncology, The First People’s Hospital of Yunnan Province, Kunming 650032, China内科片肿瘤内科云南省第一人民医院[3]Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China
Background: Lung adenocarcinoma (LUAD) is the most commonly histological subtype of lung cancer (LC) and the prognoses of the majority of LUAD patients are still very poor. The present study aimed at integrating long non-coding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) expression data to construct lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network and identify importantly potential lncRNA signature in ceRNA network as a candidate prognostic biomarker for LUAD patients. Methods: lncRNA, miRNA and mRNA expression data as well as clinical characteristics of LUAD patients were retrieved from The Cancer Genome Atlas (TCGA) database. Differentially expressed lncRNAs (DElncRNAs), differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNA (DEmiRNA) between LUAD and normal lung tissues samples were analyzed. A lncRNA-miRNA-mRNA ceRNA network was constructed and the biological functions of DEmRNAs in ceRNA network were analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Univariate and multivariate Cox regression analyses of DElncRNAs in ceRNA network were implemented to predict the overall survival (OS) in LUAD patients. The receiver operating characteristic (ROC) analysis was used to evaluate the performance of multivariate Cox regression model. Results: A total of 1,664 DElncRNAs, 120 DEmiRNAs and 2,503 DEmRNAs was identified between LUAD and normal lung tissues samples. A lncRNA-miRNA-mRNA ceRNA network including 140 DElncRNAs, 33 DEmiRNAs and 57 DEmRNAs was established. Kaplan-Meier (KM) [Log-rank (LR) test] and univariate regression analysis of those 140 DElncRNAs revealed that 7 DElncRNAs (LINC00518, UCA1, NAV2-AS2, MED4-AS1, SYNPR-AS1, AC011483.1, AP002478.1) were simultaneously identified to be associated with OS of LUAD patients. A multivariate Cox regression analysis of those 7 DElncRNAs showed that a group of 4 DElncRNAs including AP002478.1 (Cox P=4.66E-03), LINC00518 (Cox P=2.34E-04), MED4-AS1 (Cox P=6.42E-03) and NAV2-AS2 (Cox P=6.66E-02) had significantly prognostic value in OS of LUAD patients. The cumulative risk score indicated that the 4-lncRNA signature was significantly associated with OS of LUAD patients (P=0). The area under the curve (AUC) of the 4-lncRNA signature related with 3-year survival was 0.669. Conclusions: The present study provides novel insights into the lncRNA-related regulatory mechanisms in LUAD, and identifying 4-lncRNA signature may serve as a candidate prognostic biomarker in predicting the OS of LUAD patients.
基金:
This work was supported by National Natural
Science Foundation of China (grant no 31660655), Yunnan
Province Applied Basic Research Projects (grant nos
2016FB146 and 2018FE001) and Fund from Health and
Family Planning Commission of Yunnan Province (grant no
2017NS261).
第一作者机构:[1]Department of Medical Oncology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China[2]Department of Medical Oncology, The First People’s Hospital of Yunnan Province, Kunming 650032, China
共同第一作者:
通讯作者:
通讯机构:[3]Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China[*1]Faculty of Animal Science and Technology, Yunnan Agricultural University, No. 95 of Jinhei Road, Kunming 650201, China.
推荐引用方式(GB/T 7714):
Hu Jing,Wang Tonglian,Chen Qiang.Competitive endogenous RNA network identifies four long non-coding RNA signature as a candidate prognostic biomarker for lung adenocarcinoma[J].TRANSLATIONAL CANCER RESEARCH.2019,8(4):1046-+.doi:10.21037/tcr.2019.06.09.
APA:
Hu, Jing,Wang, Tonglian&Chen, Qiang.(2019).Competitive endogenous RNA network identifies four long non-coding RNA signature as a candidate prognostic biomarker for lung adenocarcinoma.TRANSLATIONAL CANCER RESEARCH,8,(4)
MLA:
Hu, Jing,et al."Competitive endogenous RNA network identifies four long non-coding RNA signature as a candidate prognostic biomarker for lung adenocarcinoma".TRANSLATIONAL CANCER RESEARCH 8..4(2019):1046-+