Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
PLoS One. 2016 Oct 4;11(10):e0163264. doi: 10.1371/journal.pone.0163264. eCollection 2016.
Circulating biomarkers can predict clinical outcomes in colorectal cancer patients. The aim of the study was to evaluate the feasibility of our multigene biomarker chip for detecting circulating tumor cells for postoperative surveillance of stage I-III colorectal cancer patients.
In total, 298 stage I-III colorectal cancer patients were analyzed after curative resection between June 2010 and October 2014. During each follow-up, a postoperative surveillance strategy, including ESMO Guidelines Working Group recommendations and the biochip, was used.
After a 28.4-month median follow-up, 48 (16.1%) patients had postoperative relapse. Univariate analysis revealed that the postoperative relapse risk factors were rectal tumor, perineural invasion, elevated preoperative and postoperative serum carcinoembryonic antigen levels, and positive biochip results (all P < 0.05). Multivariate analyses revealed that postoperative relapse correlated significantly with elevated postoperative serum carcinoembryonic antigen levels (odds ratio = 4.136, P = 0.008) and positive biochip results (odds ratio = 66.878, P < 0.001). However, the sensitivity (P = 0.003), specificity (P = 0.003), positive (P = 0.002) and negative (P = 0.006) predictive values, and accuracy (P < 0.001) of the biochip for predicting postoperative relapse were significantly higher than those of elevated postoperative serum carcinoembryonic antigen levels. Moreover, the median lead time between positive biochip result and postoperative relapse detection was significantly earlier than that between elevated postoperative serum carcinoembryonic antigen level and postoperative relapse detection (10.7 vs. 2.8 months, P < 0.001). Furthermore, positive biochip results correlated strongly with lower disease-free survival and overall survival of colorectal cancer patients (both P < 0.001).
Compared with conventional serum carcinoembryonic antigen detection, our multigene chip aided more accurate and earlier prediction of postoperative relapse during stage I-III colorectal cancer patient surveillance. In clinical practice, this biochip may facilitate early postoperative relapse diagnosis in colorectal cancer patients.
循环生物标志物可预测结直肠癌患者的临床结局。本研究旨在评估我们的多基因生物标志物芯片检测循环肿瘤细胞用于Ⅰ-Ⅲ期结直肠癌患者术后监测的可行性。
2010 年 6 月至 2014 年 10 月期间,对 298 例Ⅰ-Ⅲ期结直肠癌患者进行了根治性切除术后分析。在每次随访中,均采用术后监测策略,包括 ESMO 指南工作组的建议和生物芯片。
中位随访 28.4 个月后,48 例(16.1%)患者发生术后复发。单因素分析显示,术后复发的危险因素包括直肠肿瘤、神经周围侵犯、术前和术后血清癌胚抗原水平升高,以及生物芯片阳性(均 P<0.05)。多因素分析显示,术后复发与术后血清癌胚抗原水平升高(比值比=4.136,P=0.008)和生物芯片阳性(比值比=66.878,P<0.001)显著相关。然而,生物芯片在预测术后复发方面的敏感性(P=0.003)、特异性(P=0.003)、阳性预测值(P=0.002)、阴性预测值(P=0.006)和准确性(P<0.001)均显著高于术后血清癌胚抗原水平升高。此外,生物芯片阳性结果与术后复发检测之间的中位领先时间明显早于术后血清癌胚抗原水平升高与术后复发检测之间的中位领先时间(10.7 与 2.8 个月,P<0.001)。此外,生物芯片阳性结果与结直肠癌患者的无病生存率和总生存率显著相关(均 P<0.001)。
与传统的血清癌胚抗原检测相比,我们的多基因芯片在Ⅰ-Ⅲ期结直肠癌患者的术后监测中能更准确、更早地预测术后复发。在临床实践中,该生物芯片可能有助于早期诊断结直肠癌患者术后复发。