title: Methylation of serumSSTgene is an independent prognostic marker in colorectal cancer.
abstract: There is an increasing demand for accurate prognostication for colorectal cancer (CRC). This study sought to assess prognostic potentials of methylation targets in the serum of CRC patients. A total of 165 CRC patients were enrolled in this prospective study. Promoter methylation levels of seven genes in pre-operative sera and matched tumor tissues were evaluated by quantitative methylation-specific PCR. Kaplan-Meier test, and univariate and multivariate Cox proportional hazards regression models were used for survival analyses. After a median follow-up of 56 months, 43 patients (28.7%) experienced tumor recurrence. In univariate survival analyses, serum methylation levels ofSSTandMAL were significantly predictive of cancer-specific death (P<0.005 for both). The former was also a significant predictor for tumor recurrence (P=0.007). Independent prognostic effects of serum methylation levels ofSSTwere revealed by multivariate Cox regression model (P=0.031 andP=0.003 for cancer death and recurrence, respectively). When focusing on stage II and III patients, prognostication with serum methylatedSSTremained significant. MethylatedSSTdetected in all serum samples can be traced back to the matched primary tumor tissues. We believe that methylatedSSTdetected in the pre-operative sera of CRC patients appear to be a novel promising prognostic marker and probably can be auxiliary to tumor staging system and serum carcinoembryonic antigen towards better risk stratification.
authors.affiliation: Department of Colorectal Surgery, Singapore General Hospital Singapore.
authors.forename: Yanqun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Colorectal Surgery, Singapore General Hospital Singapore.
authors.forename: Min Hoe
authors.initials: MH
authors.lastname: Chew
authors.affiliation: Department of Medical Oncology, National Cancer Centre of Singapore Singapore.
authors.forename: Chee Kian
authors.initials: CK
authors.lastname: Tham
authors.affiliation: Department of Colorectal Surgery, Singapore General Hospital Singapore.
authors.forename: Choong Leong
authors.initials: CL
authors.lastname: Tang
authors.affiliation: Department of Medical Oncology, National Cancer Centre of Singapore Singapore.
authors.forename: Simon Yk
authors.initials: SY
authors.lastname: Ong
authors.affiliation: Department of Clinical Research, Singapore General Hospital Singapore.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
keywords: Blood biomarker; DNA methylation; SST; cell free DNA; colorectal cancer; disease-free surviva; prognosis