Abstract
PurposeThis study aimed to construct an m6A-related long non-coding RNAs (lncRNAs) signature to accurately predict the prognosis of kidney clear cell carcinoma (KIRC) patients using data obtained from The Cancer Genome Atlas (TCGA) database.MethodsThe KIRC patient data were downloaded from TCGA database and m6A-related genes were obtained from published articles. Pearson correlation analysis was implemented to identify m6A-related lncRNAs. Univariate, Lasso, and multivariate Cox regression analyses were used to identifying prognostic risk-associated lncRNAs. Five lncRNAs were identified and used to construct a prognostic signature in training set. Kaplan–Meier curves and receiver operating characteristic (ROC) curves were applied to evaluate reliability and sensitivity of the signature in testing set and overall set, respectively. A prognostic nomogram was established to predict the probable 1-, 3-, and 5-year overall survival of KIRC patients quantitatively. GSEA was performed to explore the potential biological processes and cellular pathways. Besides, the lncRNA/miRNA/mRNA ceRNA network and PPI network were constructed based on weighted gene co-expression network analysis (WGCNA). Functional Enrichment Analysis was used to identify the biological functions of m6A-related lncRNAs.ResultsWe constructed and verified an m6A-related lncRNAs prognostic signature of KIRC patients in TCGA database. We confirmed that the survival rates of KIRC patients with high-risk subgroup were significantly poorer than those with low-risk subgroup in the training set and testing set. ROC curves indicated that the prognostic signature had a reliable predictive capability in the training set (AUC = 0.802) and testing set (AUC = 0.725), respectively. Also, we established a prognostic nomogram with a high C-index and accomplished good prediction accuracy. The lncRNA/miRNA/mRNA ceRNA network and PPI network, as well as functional enrichment analysis provided us with new ways to search for potential biological functions.ConclusionsWe constructed an m6A-related lncRNAs prognostic signature which could accurately predict the prognosis of KIRC patients.
Highlights
Renal cell carcinoma (RCC) was the third most common malignant tumor of the urinary system worldwide [1], of which kidney renal clear cell carcinoma (KIRC) was the most frequent subtype [2]
This study aimed to construct an m6A-related long non-coding RNAs signature to accurately predict the prognosis of kidney clear cell carcinoma (KIRC) patients using data obtained from The Cancer Genome Atlas (TCGA) database
We constructed an m6A-related long non-coding RNA (lncRNA) prognostic signature which could accurately predict the prognosis of KIRC patients
Summary
Renal cell carcinoma (RCC) was the third most common malignant tumor of the urinary system worldwide [1], of which kidney renal clear cell carcinoma (KIRC) was the most frequent subtype [2]. DNA methylation and post-translational histone modifications were involved in the epigenetic regulation of cell development and differentiation [5]. The m6A modifications were regulated by m6A regulators, including methyltransferases complex (“writers”), signal transducers (“readers”), and demethylases (“erasers”) [8]. Cai et al [9] reported that m6A Methyltransferase METTL3 promoted the growth of prostate cancer by regulating hedgehog pathway. Guo et al [10] reported that RNA demethylases ALKBH5 prevented pancreatic cancer progression by post-transcriptional activation of PER1. Zhuang et al [11] reported that FTO suppressed KIRC progression through the FTO-PGC-1a signaling pathway. Gao et al [12] reported that DMDRMR-mediated regulation of CDK4 promoted KIRC progression through m6A reader IGF2BP3
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