DNA Methylation Biomarkers Predict Progression-Free and Overall Survival of Metastatic Renal Cell Cancer (mRCC) Treated with Antiangiogenic Therapies

• DOI: 10.1371/journal.pone.0091440
• Publication Date: 2014-03-14T20:28:32Z
• Authors: Inga Peters; Natalia Dubrowins...; Mahmoud Abbas; Christoph Seidel; Michael Kogosov; Ralph Scherer; Kai Gebauer; Axel S. Merseburger; Markus A. Kuczyk; Viktor Grünwald; Jürgen Serth
• Keywords: CpG site; Progression-free survival

VEGF-targeted therapy increases both the progression-free (PFS) and overall survival (OS) of patients with metastasized renal cell cancer (mRCC). Identification molecular phenotypes RCC could improve risk-stratification prediction clinical disease course. We investigated whether gene-specific DNA hypermethylation can predict PFS OS among undergoing anti-VEGF-based therapy. Primary tumor tissues from 18 receiving targeted were examined retrospectively using quantitative methylation-specific PCR analysis CST6, LAD1, hsa-miR-124-3, hsa-miR-9-1 CpG islands. analyzed for first-line sequential antiangiogenic therapies log rank statistics. Sensitivity specificity determined predicting failure. Hypermethylation CST6 LAD1 was associated a shortened (log p = 0.009 0.004) (p 0.011 0.043). The median observed high low methylation groups 2.0 vs.11.4 months. had 1.0 (95% CI 0.65–1.0) sensitivity 0.73 0.43–0.90) are candidate epigenetic biomarkers showing unprecedented association as well response to markers should be considered prospective evaluation larger patient cohorts in future studies.