DNA hypermethylation in papillary renal cell carcinoma

Abstract

a specificity of 73.3% as determined via receiver operator characteristic analysis (area under curve = 0.814). Hypermethylation at APC (3.0 vs 6.7%), CDH1 (15.6 vs 0%), GSTP1 (21.9 vs 6.7%) and TIMP3 (6.3 vs 0%) was infrequent in pRCC and normal tissue. CDH1 was significantly correlated with pathological stage ( P = 0.015), and patients with methylated CDH1 methylation showed a trend towards shorter recurrence-free survival (log-rank P = 0.057). The number of methylated gene sites was correlated with pathological stage ( P = 0.007) and lymph node metastasis ( P = 0.008). CONCLUSIONSDNA hypermethylation at RASSF1A is common in pRCC tissue irrespective of the histological subtype, but also frequently seen at lower levels in normal adjacent tissue. Aberrant hypermethylation could be a prognostic marker for pRCC.

Association between RASSF1A promoter methylation and renal cell cancer susceptibility: a meta-analysis

“…Ten studies were excluded because they were laboratory studies, non-original articles (reviews), or studies irrelevant to the current analysis. Eventually, 13 publications were included in the final meta-analysis (Yoon et al, 2001;Morrissey et al, 2001;Ehrlich et al, 2002;Harada et al, 2002;Wagner et al, 2002;Dulaimi et al, 2004;Gonzalgo et al, 2004;Loginov et al, 2004;Tokinaga et al, 2004;Costa et al, 2007;Duan Jianmin, 2007;Zhang Jian-Ying, 2008;Ellinger et al, 2011).…”

Prognostic DNA Methylation Markers for Renal Cell Carcinoma: A Systematic Review

“…Promoter methylation of LAD1 [31,39] and NEFH [31,40] not only predicted patient survival, but also response to treatment with antiangiogenic agents. Conflicting results regarding the prognostic value of promoter methylation of SFRP1 [27][28][29], PCDH8 [29,32,38], GREM1 [27,[29][30] and RASSF1A [26,[35][36][37] were found. Several reasons for these inconsistent results can be adduced.…”

“…This is important as the prognostic value of the studied methylation marker can vary according to the specific tumor subtype, which was demonstrated for methylation of RASSF1A [26,[35][36][37]. Furthermore, only 30% of the studies specified whether patients had received systemic treatment.…”

“…Whereas Ellinger and colleagues [35] and Kawai and colleagues [36] were able to link promoter methylation of RASSF1A to shorter PFS in papillary RCC (p = 0.046) and shorter disease-specific survival (DSS) in ccRCC (multivariate HR: 1.78, 95% CI: 1.18-2.78, p = 0.0053), respectively, de Martino et al [26] could not find such an association when studying promoter methylation in cell-free DNA derived from blood samples from patients with various subtypes of RCC (p = 0.232). Recently, Klacz et al [37] found that promoter methylation of RASSF1A was associated with worse OS in patients with ccRCC in univariate analyses (HR: 3.00; 95% CI: 1.18-7.65; p = 0.02), however, this association was lost when correcting for tumor stage and grade in multivariate analyses (Supplementary Table 5 & Figure 4F).…”

“…For several other genes statistically significant associations between methylation and patient survival were found, but were only reported in a single study [27,31,39,, and for some other genes null associations were reported [26][27]32,[34][35]39,42,[67][68][69][70] (Figure 3 & Supplementary Table 4).…”