A nomogram based on 9-lncRNAs signature for improving prognostic prediction of clear cell renal cell carcinoma

Wen Jiang,Yu Zhu,Chenghe Wang,Qing Guo

doi:10.1186/s12935-019-0928-5

Abstract

BackgroundAbnormal expressions of long noncoding RNAs (lncRNAs) are very common in clear cell renal cell carcinoma (ccRCC), and some of these have been reported to be highly correlated with prognosis of ccRCC patients.Methods“edgeR” AND “DEseq” R packages were used to explore differentially expressed genes (DEGs) between normal and tumor tissues of ccRCC samples from The Cancer Genome Atlas (TCGA). Univariable Cox survival analysis, robust likelihood-based survival model and multivariable Cox regression analysis were used to identify prognostic lncRNAs and construct lncRNAs signature. Finally, a graphic nomogram based on the lncRNAs signature was developed to predict 1-, 3- and 5-year survival probability of ccRCC patients by using rms R package.Results8413 DEGs including 2740 lncRNAs and 4530 mRNAs were identified between normal and tumor tissues. 395 lncRNAs were found to be associated with prognosis of ccRCC patients (P < 0.05). Among these 395 prognostic lncRNAs, 9 key prognostic lncRNAs (RP13-463N16.6, CTD-2201E18.5, RP11-430G17.3, AC005785.2, RP11-2E11.9, TFAP2A-AS1, RP11-133F8.2, RP11-297L17.2 and RP11-348J24.2) were identified by using robust likelihood-based survival model. A 9-lncRNAs signature was constructed by using estimated regression coefficients of the 9 key prognostic lncRNAs. Results of χ2-test or Fisher’s exact test indicated that the 9-lncRNAs signature was significantly associated with clinicopathological characteristics such as tumor grade, T stage, N stage, M stage, TNM stage and survival outcome of ccRCC patients. Multivariate analysis showed that the 9-lncRNAs signature, age and M stage were independent prognostic factors. Finally, a graphic nomogram based on the lncRNAs signature, age and M stage was developed to predict 1-, 3- and 5-year survival probability of ccRCC patients by using rms R package.ConclusionsA 9-lncRNAs signature associated with prognosis of ccRCC patients was constructed and a promising prognostic nomogram based on the 9-lncRNAs signature was developed for 1-, 3- and 5-year OS prediction of ccRCC patients in this study.

Highlights

Abnormal expressions of long noncoding RNAs are very common in clear cell renal cell carcinoma, and some of these have been reported to be highly correlated with prognosis of Clear cell renal cell carcinoma (ccRCC) patients
The 9‐long noncoding RNAs (lncRNAs) signature is an independent prognostic factor in ccRCCBy χ2-test or Fisher’s exact test, we found that the 9-lncRNAs signature was significantly associated with tumor grade, T stage, N stage, M stage, TNM stage and survival status of ccRCC patients (Table 3)
The results indicated that 9-lncRNAs signature was a fine prognostic predictor which was independent of TNM staging system

Summary

Introduction

Abnormal expressions of long noncoding RNAs (lncRNAs) are very common in clear cell renal cell carcinoma (ccRCC), and some of these have been reported to be highly correlated with prognosis of ccRCC patients. Stage, Size, Grade, and Necrosis (SSIGN) Score system, which was firstly reported in 2002 for outcome prediction of ccRCC patients, has been proved to have better predictive ability than TNM staging system [5]. Another staging system consisted of tumor grade, N stage and patients’ performance status could accurately distinguish RCC patients with different survival possibility [6]. These systems included parameters depended on subjective judgement of professional pathologist, and they made prediction even influenced by inter-observer variabilities. More concise and practical tools are urged for improving prognostic prediction of ccRCC patients

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Discussion

Conclusion