Methylation of helicase-like transcription factor in serum of patients with colorectal cancer is an independent predictor of disease recurrence.
BACKGROUND
CpG island hypermethylation is a common epigenetic event in colorectal cancer. The presence of simultaneous methylation of multiple genes is associated with poor prognosis in many types of tumours including colorectal cancer. We have shown earlier that the hypermethylation of the genes HLTF and HPP1/TPEF are independent prognostic serum markers in colorectal cancer identifying patients with increased risk of death. The purpose of this study was to analyse whether these factors also identify patients at risk of disease recurrence after curative surgery.


METHODS
Pretherapeutic sera of 106 patients curatively resected for colorectal cancer with known 5-year follow-ups were analysed for the presence of methylation of the genes HLTF and HPP1/TPEF.


RESULTS
HLTF serum methylation was associated with an increased risk of disease recurrence by a factor of 2.7 (95% confidence interval: 1.2-6.0; P=0.014). Multivariate analysis showed methylated HLTF serum DNA to be independently associated with poor outcome and a relative risk of disease recurrence of 2.5 (95% confidence interval: 1.1-5.6; P=0.023).


CONCLUSIONS
Here, we show for the first time that a DNA methylation-based surrogate marker can serve as a predictor of disease recurrence in colorectal cancer.
Herbst
Andreas
A
Department of Medicine II, University Hospital Grosshadern, University of Munich, Munich, Germany.
Wallner
Maike
M
Rahmig
Konstanze
K
Stieber
Petra
P
Crispin
Alexander
A
Lamerz
Rolf
R
Kolligs
Frank T
FT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C100023:HLTF protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C423567:TMEFF2 protein, human; D014157:Transcription Factors