Wnt antagonist family genes as biomarkers for diagnosis, staging, and prognosis of renal cell carcinoma using tumor and serum DNA.

Wnt antagonist family genes as biomarkers for diagnosis, staging, and prognosis of renal cell carcinoma using tumor and serum DNA. Research Abstract Details 

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Wnt antagonist family genes as biomarkers for diagnosis, staging, and prognosis of renal cell carcinoma using tumor and serum DNA. Abstract Text:

Shinji Urakami,Hiroaki Shiina,Hideki Enokida,Hiroshi Hirata,Ken Kawamoto,Toshifumi Kawakami,Nobuyuki Kikuno,Yuichiro Tanaka,Shahana Majid,Masayuki Nakagawa,Mikio Igawa,Rajvir Dahiya,

PURPOSE: We hypothesized that combined methylation analysis of Wnt antagonist genes could serve as a panel of biomarkers for diagnosis, staging, and prognosis in renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: Samples (n = 62) of RCC and corresponding normal renal tissue (NRT) were analyzed using methylation-specific PCR for methylation of six Wnt antagonist genes (sFRP-1, sFRP-2, sFRP-4, sFRP-5, Wif-1, and Dkk-3). To increase the sensitivity/specificity of RCC detection, the methylation score (M score) for multigene methylation analysis was developed. Receiver operator characteristic curve analysis was used to determine the optimal sensitivity/specificity of the M score. In addition, the M score was compared with the clinicopathologic outcome. Thirty-three serum DNA samples were also used to investigate the methylation status of Wnt antagonist genes. RESULTS: The methylation levels of all Wnt antagonists were significantly higher in RCC than in NRT. In multivariate regression analysis, the methylation level of sFRP-1 was a significant independent predictor of RCC, whereas for sFRP-2 and sFRP-4 there was a trend toward significance as independent predictors. The M score of Wnt antagonist genes was significantly higher in RCC than in NRT. Overall, the M score had a sensitivity of 79.0% and a specificity of 75.8% (area under the curve, 0.808) as a diagnostic biomarker. In addition, the M score could significantly distinguish grade, pT category, M category, and overall survival of RCC patients. The M score was independent of age and gender in predicting overall survival by the Cox proportional hazards model. In RCC patients, 72.7% of the methylation-specific PCR results had identical methylation in samples of tumor and serum DNA. No serum DNA in normal controls showed aberrant methylation of the Wnt antagonist genes. In addition, the methylation status of Wnt antagonist genes in serum DNA was significantly correlated with tumor grade and stage. CONCLUSIONS: This is the first report showing that M score analysis of Wnt antagonist genes can serve as an excellent epigenetic biomarker panel for detection, staging, and prognosis of RCC using serum DNA.

Wnt antagonist family genes as biomarkers for diagnosis, staging, and prognosis of renal cell carcinoma using tumor and serum DNA. Publishing Authors By Initials

S Urakami,H Shiina,H Enokida,H Hirata,K Kawamoto,T Kawakami,N Kikuno,Y Tanaka,S Majid,M Nakagawa,M Igawa,R Dahiya,

For similar biological factors: biological markers: tumor markers, biological research abstracts see: biological factors: biological markers: tumor markers, biological research

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Wnt antagonist family genes as biomarkers for diagnosis, staging, and prognosis of renal cell carcinoma using tumor and serum DNA. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Clinical cancer research : an official journal of

VOLUME: 12

Page Numbers: 6989-97

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 1

MONTH: Dec

YEAR: 2006

Wnt antagonist family genes as biomarkers for diagnosis, staging, and prognosis of renal cell carcinoma using tumor and serum DNA. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9502500

Wnt antagonist family genes as biomarkers for diagnosis, staging, and prognosis of renal cell carcinoma using tumor and serum DNA. Keywords Mesh Terms:

KEYWORDS: Tumor Markers, Biological

MESH TERMS: genetics

Chemical & Substance for Abstract: Wnt antagonist family genes as biomarkers for diagnosis, staging, and prognosis of renal cell carcinoma using tumor and serum DNA. Information

Substance Name: WIF1 protein, human

Registry Number: 0

Grant and Affiliation Information for Wnt antagonist family genes as biomarkers for diagnosis, staging, and prognosis of renal cell carcinoma using tumor and serum DNA.

AFFILIATION: Department of Urology, Veterans Affairs Medical Center, University of California, San Francisco, California 94121, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: T32DK07790

ACRONYM: DK

MEDLINETA: Clin Cancer Res

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