Correlation of Circulating Angiogenic Factors with Circulating Tumor Cells and Disease Recurrence in Patients Undergoing Curative Resection for Colorectal Liver Metastases

Abstract

Circulating angiogenic factors (CAF) have been shown as therapeutic targets and prognostic biomarkers in metastatic colorectal cancer. However, their correlation with circulating tumor cells (CTC) is unknown, as is their role as prognostic biomarkers in patients amenable for curative resection. Preoperative blood samples were collected in patients undergoing potentially curative resection of colorectal liver metastases. Serum levels of eight CAF and CTC were analyzed by using ELISA and CK20 RT-PCR, respectively. Prognostic factors were identified by a Cox proportional hazards model. A total of 107 patients were eligible for final analyses. Circulating levels of PlGF, EGF, and bFGF were increased, whereas PDGF-A and Ang-1 levels were decreased in patients compared with healthy control subjects. CTC were detected in 36 of 63 patients (57%) and were associated with significantly lower levels of EGF and bFGF. On univariate analyses, multiple metastases (p = 0.04), a MSKCC risk score >2 (p = 0.004), and detection of CTC (p = 0.05) were associated with disease recurrence. Multivariate analysis, including the panel of eight CAF, revealed a MSKCC score >2 [hazard ratio (HR), 2.01; 95% confidence interval (CI), 1.11-3.82; p = 0.02] and low levels of circulating PlGF (HR, 0.26; 95% CI, 0.08-0.81; p = 0.02) as independent predictors of poor recurrence-free survival. CAF may indicate patients who are at high risk for disease recurrence. The notion that CAF may identify patients who benefit from adjuvant therapy or antiangiogenic agents warrants further investigation.