A Prospective Study of Comparing Multi-Gene Biomarker Chip and Serum Carcinoembryonic Antigen in the Postoperative Surveillance for Patients with Stage I-III Colorectal Cancer

PLoS One. 2016 Oct 4;11(10):e0163264. doi: 10.1371/journal.pone.0163264. eCollection 2016.

Abstract

Background: 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.

Materials and methods: 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.

Results: 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).

Conclusion: 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.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Carcinoembryonic Antigen / blood*
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Patient Outcome Assessment
  • Postoperative Period
  • Prognosis
  • Prospective Studies
  • ROC Curve
  • Recurrence
  • Tumor Burden

Substances

  • Biomarkers, Tumor
  • Carcinoembryonic Antigen

Grants and funding

This work was supported by Ministry of Science and Technology, Taiwan MOST1042325B037001 Prof. JawYuan Wang, Ministry of Health and Welfare MOHW105TDUB212134007 Prof. JawYuan Wang, Kaohsiung Medical University Hospital KMUH102-2M26, KMUH104-4R19, KMUHS10522, KMUHS10505 Prof. JawYuan Wang, Kaohsiung Medical University KMU-TP105C00, KMU-TP105C01, KMU-TP105C02, KMU-TP106005, D08-00005-10401, KMU-TP105A12 Prof. JawYuan Wang.