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Full-Length Enrich c-DNA Libraries-Clear Cell-Renal Cell Carcinoma.

ABSTRACT: Clear cell renal cell carcinoma (ccRCC), the most common subtype of RCC, is characterized by high metastasis potential and strong resistance to traditional therapies, resulting in a poor five-year survival rate of patients. Several therapies targeted to VEGF pathway for advanced RCC have been developed, however, it still needs to discover new therapeutic targets for treating RCC. Genome-wide gene expression analyses have been broadly used to identify unknown molecular mechanisms of cancer progression. Recently, we applied the oligo-capping method to construct the full-length cDNA libraries of ccRCC and adjacent normal kidney, and analyzed the gene expression profiles by high-throughput sequencing. This paper presents a review for recent findings on therapeutic potential of MYC pathway and nicotinamide N-methyltransferase for the treatment of RCC.

SUBMITTER: Tang SW

PROVIDER: S-EPMC3321460 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Full-Length Enrich c-DNA Libraries-Clear Cell-Renal Cell Carcinoma.

Tang Sai-Wen SW Lin Jung-Yaw JY

Journal of oncology 20120320

Clear cell renal cell carcinoma (ccRCC), the most common subtype of RCC, is characterized by high metastasis potential and strong resistance to traditional therapies, resulting in a poor five-year survival rate of patients. Several therapies targeted to VEGF pathway for advanced RCC have been developed, however, it still needs to discover new therapeutic targets for treating RCC. Genome-wide gene expression analyses have been broadly used to identify unknown molecular mechanisms of cancer progre ...[more]

PMID: 22545051

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Project description:BackgroundClear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cancer and is associated with poor prognosis if metastasized. Up to one third of patients with local disease at diagnosis will develop metastasis after nephrectomy, and there is a need for new molecular markers to identify patients with high risk of tumor progression. In the present study, we performed genome-wide promoter DNA methylation analysis at diagnosis to identify DNA methylation profiles associated with risk for progress.MethodDiagnostic tissue samples from 115 ccRCC patients were analysed by Illumina HumanMethylation450K arrays and methylation status of 155,931 promoter associated CpGs were related to genetic aberrations, gene expression and clinicopathological parameters.ResultsThe ccRCC samples separated into two clusters (cluster A/B) based on genome-wide promoter methylation status. The samples in these clusters differed in tumor diameter (p < 0.001), TNM stage (p < 0.001), morphological grade (p < 0.001), and patients outcome (5 year cancer specific survival (pCSS5yr) p < 0.001 and cumulative incidence of progress (pCIP5yr) p < 0.001. An integrated genomic and epigenomic analysis in the ccRCCs, revealed significant correlations between the total number of genetic aberrations and total number of hypermethylated CpGs (R = 0.435, p < 0.001), and predicted mitotic age (R = 0.407, p < 0.001). We identified a promoter methylation classifier (PMC) panel consisting of 172 differently methylated CpGs accompanying progress of disease. Classifying non-metastatic patients using the PMC panel showed that PMC high tumors had a worse prognosis compared with the PMC low tumors (pCIP5yr 38% vs. 8%, p = 0.001), which was confirmed in non-metastatic ccRCCs in the publically available TCGA-KIRC dataset (pCIP5yr 39% vs. 16%, p < 0.001).ConclusionDNA methylation analysis at diagnosis in ccRCC has the potential to improve outcome-prediction in non-metastatic patients at diagnosis.

Dataset Information

Full-Length Enrich c-DNA Libraries-Clear Cell-Renal Cell Carcinoma.

Publications

Full-Length Enrich c-DNA Libraries-Clear Cell-Renal Cell Carcinoma.

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