Clear cell renal cell carcinoma (ccRCC) is the most common and invasive histological subtype of all kidney malignancies, with high levels of incidence and mortality. In the present study, long non-coding (lnc)RNA expression profiles of patients with ccRCC from The Cancer Genome Atlas database were comprehensively analyzed to identify differentially expressed lncRNAs (DElncRNAs). The patients with ccRCC were then divided into training and validation cohorts. Univariate and LASSO regression analyses were performed to select the most significant survival-associated candidate DElncRNAs in the training cohort. Multivariate Cox regression analysis was then performed to develop a risk score formula and a prognostic nomogram for predicting 3- and 5-year overall survival (OS). The accuracies of the nomogram predictions were evaluated by determining the area under the receiver operating characteristic curve (AUC) and a calibration plot. Finally, functional enrichment analysis and protein-protein interaction network prediction were implemented to predict the functions and molecular mechanisms of the candidate DElncRNAs in ccRCC. A total of 1,553 DElncRNAs were identified, and 5 candidate DElncRNAs (AC026992.2, AC245041.2, LINC00524, LINC01956 and LINC02080) were included in the nomogram. The AUC values for 3- and 5-year overall survival in the training cohort were 0.768 and 0.814, respectively, which were increased compared with that based on the clinical index (0.760 and 0.694, respectively). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that the 521 mRNAs highly associated with 5 DElncRNAs were primarily involved in 17 terms and 25 pathways, respectively. Based on the 5 DElncRNAs, a novel and convenient prognostic nomogram for predicting 3- and 5-year OS for patients with ccRCC was developed. The results of the present study may be conducive to the development of a precise predictive tool for the prognosis of ccRCC and may provide information regarding the molecular mechanisms of ccRCC. However, additional experimental in vitro and in vivo studies investigating lncRNAs may be required.
Oncology letters. 2019 Oct 18 [Epub]
Sheng Wang, Kequn Chai, Jiabin Chen
The Second Clinical Medical College, Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310053, P.R. China., Department of Oncology, Tongde Hospital of Zhejiang, Hangzhou, Zhejiang 310012, P.R. China.