Abstract
BackgroundRenal cell carcinoma (RCC) account for over 80% of renal malignancies. The most common type of RCC can be classified into three subtypes including clear cell, papillary and chromophobe. ccRCC (the Clear Cell Renal Cell Carcinoma) is the most frequent form and shows variations in genetics and behavior. To improve accuracy and personalized care and increase the cure rate of cancer, molecular typing for individuals is necessary.MethodsWe adopted the genome, transcriptome and methylation HMK450 data of ccRCC in The Cancer Genome Atlas Network in this research. Consensus Clustering algorithm was used to cluster the expression data and three subtypes were found. To further validate our results, we analyzed an independent data set and arrived at a consistent conclusion. Next, we characterized the subtype by unifying genomic and clinical dimensions of ccRCC molecular stratification. We also implemented GSEA between the malignant subtype and the other subtypes to explore latent pathway varieties and WGCNA to discover intratumoral gene interaction network. Moreover, the epigenetic state changes between subgroups on methylation data are discovered and Kaplan-Meier survival analysis was performed to delve the relation between specific genes and prognosis.ResultsWe found a subtype of poor prognosis in clear cell renal cell carcinoma, which is abnormally upregulated in focal adhesions and cytoskeleton related pathways, and the expression of core genes in the pathways are negatively correlated with patient outcomes.ConclusionsOur work of classification schema could provide an applicable framework of molecular typing to ccRCC patients which has implications to influence treatment decisions, judge biological mechanisms involved in ccRCC tumor progression, and potential future drug discovery.
Highlights
Renal cell carcinoma (RCC) account for over 80% of renal malignancies
Most people with kidney cancer are usually over 55 years of ages and this cancer is more common in men [1].The global pattern of genetic changes underlying Clear Cell Renal Cell Carcinoma (ccRCC) includes alterations in genes controlling cellular oxygen sensing and the maintenance of chromatin states [2]
Intratumoral gene interaction network in EC1 relates to cell adhesion and motion After obtaining the relative enrichment pathways in EC1, we aim to investigate the intratumoral gene interaction network
Summary
Renal cell carcinoma (RCC) account for over 80% of renal malignancies. The most common type of RCC can be classified into three subtypes including clear cell, papillary and chromophobe. CcRCC (the Clear Cell Renal Cell Carcinoma) is the most frequent form and shows variations in genetics and behavior. CcRCC, the most common type of kidney cancer, representing approximately 92% of such cases. Most people with kidney cancer are usually over 55 years of ages and this cancer is more common in men [1].The global pattern of genetic changes underlying ccRCC includes alterations in genes controlling cellular oxygen sensing and the maintenance of chromatin states [2]. Wu et al BMC Cancer (2018) 18:287 with the other and find some pathways changes and genes that may cause adverse outcomes
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