title: Postoperative serum methylation levels of TAC1 and SEPT9 are independent predictors of recurrence and survival of patients with colorectal cancer.
abstract: BACKGROUND
  Serum carcinoembryonic antigen (CEA) is the only marker recommended for surveillance of colorectal cancer (CRC) recurrence; its sensitivity and specificity, however, are suboptimal. This study sought to evaluate the values of postoperative serum methylation levels of 7 genes for prognostication and especially for recurrence detection after curative resection.
  
  
  METHODS
  This prospective cohort study included 150 patients with stage I-III CRC from whom 3 consecutive blood sampling was taken 1 week before, and 6 months and 1 year after operation. Methylation levels of 7 genes were evaluated via quantitative methylation-specific polymerase chain reaction. Serum CEA was measured in parallel. Univariate and multivariate survival analyses were followed by construction of receiver operating characteristic curves for recurrence detection.
  
  
  RESULTS
  After a median follow-up of 59 months, 43 patients (28.7%) developed recurrent lesions. High serum methylation levels of TAC1 in serum at 6-month follow-up (6M-FU), and SEPT9 at 1-year follow-up (1Y-FU) were independent predictors for tumor recurrence and unfavorable cancer-specific survival (CSS) (P < .05 in all tests). Serum NELL1 methylation levels were significant alone for CSS at both 6M-FU and 1Y-FU, but not for disease-free survival. Dynamic changes of TAC1 and SEPT9 with methylation increment were also independently predictive for recurrence (P < .05 in all tests). More importantly, TAC1 at 6M-FU and SEPT9 at 1Y-FU exhibited earlier detection of potential recurrences compared with concurrent serum CEA.
  
  
  CONCLUSIONS
  Levels of TAC1 and SEPT9 methylation detected in postoperative sera of patients with CRC appear to be novel promising prognostic markers and may probably be considered for monitoring of CRC recurrence.
authors.affiliation: Department of Medical Oncology, National Cancer Centre of Singapore, Singapore.
authors.forename: CheeKian
authors.initials: C
authors.lastname: Tham
authors.forename: MinHoe
authors.initials: M
authors.lastname: Chew
authors.forename: Richie
authors.initials: R
authors.lastname: Soong
authors.forename: JitFong
authors.initials: J
authors.lastname: Lim
authors.forename: MeiKim
authors.initials: M
authors.lastname: Ang
authors.forename: ChoongLeong
authors.initials: C
authors.lastname: Tang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Simon Y K
authors.initials: SY
authors.lastname: Ong
authors.forename: Yanqun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000097:blood; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D019175:DNA Methylation; D018572:Disease-Free Survival; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000235:genetics; D011184:Postoperative Period; D011379:Prognosis; D011446:Prospective Studies; D058112:Septins / Q000097:blood* / Q000235:genetics; D015320:Tachykinins / Q000097:blood* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D015320:Tachykinins; C474315:SEPTIN9 protein, human; D058112:Septins
keywords: blood markers; cancer recurrence; early diagnosis; epigenetics