Persistent Presence of Postoperative Circulating Tumor Cells is a Poor Prognostic Factor for Patients with Stage I–III Colorectal Cancer after Curative Resection
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To detect pre- and postoperative circulating tumor cells (CTCs) in stage I–III colorectal cancer (CRC) patients undergoing curative resection and so identify a subgroup of patients who are at high risk for relapse.
Four mRNA molecular markers including human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen mRNA were used to detect CTCs in 438 CRC patients underwent curative resection.
Out of 438 patients, 80 CRC patients were classified to preoperative (−)/postoperative (−), 221 patients were preoperative (+)/postoperative (−), while 137 patients were preoperative (+)/postoperative (+). Univariately, postoperative relapse was significantly correlated with depth of invasion (P = 0.032), lymph node metastasis (P < 0.001), vascular invasion (P = 0.001), perineural invasion (P = 0.013), and persistent presence of CTCs (P < 0.001). Using a multivariate proportional hazards regression analysis, the presence of lymph node metastasis (P = 0.012; HR, 7.652; 95% CI: 4.162–14.827), vascular invasion (P = 0.033; HR, 4.360; 95% CI: 2.793–10.847), and the persistent presence of CTCs (P < 0.001; HR, 29.486; 95% CI: 10.281–87.792) were demonstrated to be independent predictors for postoperative relapse. Combination of these three independent predictors showed that patients with any one positive predictor had a hazard ratio of sevenfold to develop postoperative relapse (P < 0.001; HR, 7.064; 95% CI: 4.354–11.464). Furthermore, the persistent presence of CTCs was strongly correlated with poorer relapse-free survival rates (all P < 0.001).
The promising results of this study suggest that persistent presence of postoperative CTCs may be a crucial prognostic factor adjuvant to conventional tumor markers in CRC patients who have undergone curative resection. Identification of these high-risk patients of persistent CTCs positivity is important and thus could help to define patients for adjuvant therapy with this tumor entity.
KeywordsCirculating tumor cells Molecular markers Colorectal cancer Prognosis Postoperative surveillance
The authors would like to thank Drs. Jan-Sing Hsieh, Deng-Chyang Wu, Yu-Chung Su, Jeng-Yih Wu, and Che-Jen Huang for contributing materially to the paper. This study was supported by a grant from the Chi Mei Medical Center and Kaohsiung Medical University Research Foundation (97CM-KMU-03).
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