Methylation level of the RASSF1A promoter is an independent prognostic factor for clear-cell renal cell carcinoma.
BACKGROUND
Ras association domain family 1A (RASSF1A) is a tumor suppressor that regulates the cell cycle, apoptosis, and microtubule stability. The association between the methylation levels of RASSF1A and the prognosis of clear-cell renal cell carcinoma (CCRCC) remains unclear. Therefore, we investigated this relationship to determine the prognostic value of RASSF1A methylation levels for CCRCC.


METHODS
The study comprised 179 Japanese patients who underwent radical or partial nephrectomy for CCRCC. The methylation level of 5' CpG islands in the RASSF1A was evaluated using combined bisulfite restriction analysis and bisulfite sequencing.


RESULTS
High levels of methylation in the RASSF1A promoter were significantly more frequent in grade 3 compared with grade 1 or 2 tumors (P = 0.028) and in patients with stage III or IV compared with patients with stage I or II (P = 0.043). Patients with high methylation levels had a significantly less favorable prognosis compared with those with low methylation levels (P = 0.040). Higher methylation levels were independently associated with a poor prognosis following multivariate analysis (P = 0.0053).


CONCLUSIONS
These results indicate that quantitative promoter methylation levels of the RASSF1A gene may be a useful marker to predict the prognosis of CCRCC.
Kawai
Y
Y
Department of Urology.
Sakano
S
S
Department of Urology. Electronic address: shigerus@yamaguchi-u.ac.jp.
Suehiro
Y
Y
Department of Oncology and Laboratory Medicine, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
Okada
T
T
Department of Oncology and Laboratory Medicine, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
Korenaga
Y
Y
Department of Urology.
Hara
T
T
Department of Urology.
Naito
K
K
Department of Urology.
Matsuyama
H
H
Department of Urology.
Hinoda
Y
Y
Department of Oncology and Laboratory Medicine, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins