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. Cancer 2014;120:3131-41.

A cross‐sectional study comparing a blood test for methylated BCAT1 and IKZF1 tumor‐derived DNA with CEA for detection of recurrent colorectal cancer

“…In‐so‐far as a modest survival benefit with CEA testing as part of a surveillance protocol has been observed , and that the BCAT1/IKZF1 test is more sensitive for recurrence in our study, then definitive studies aimed at assessing potential survival benefit with the BCAT1/IKZF1 test are now indicated. There might also be potential for prediction of prognosis independent of stage, as has been reported for other biomarkers .…”

Promoter hypermethylation of SHOX2 and SEPT9 is a potential biomarker for minimally invasive diagnosis in adenocarcinomas of the biliary tract

“…Furthermore, an increased methylation level of SEPT9 was a predictor of poor prognosis in esophageal squamous cell carcinoma, as well as in prostate cancer on androgen deprivation [52, 53]. Likewise, colorectal cancer patients with high SEPT9 serum methylation levels at 1-year follow-up were found to be at high risk of disease recurrence [64]. Although these promising findings in other cancer entities suggested that aberrant SHOX2 and SEPT9 methylation may also correlate with prognosis in BTC, our results did not confirm this hypothesis.…”

Circulating tumour cells and DNA as liquid biopsies in gastrointestinal cancer

“…The prognostic impact of ctDNA analysis has been demonstrated in several studies of both localized and metastatic colorectal cancer. In a seminal study, Tie and colleagues detected ctDNA after operation in 20 (8.7 per cent) of 230 patients with stage II colorectal cancer by the Safe‐SeqS NGS method.…”