Plasma Prokineticin 1, a prognostic biomarker in colorectal cancer patients with curative resection: a retrospective cohort study

Abstract

Background: Prokineticin 1 (PROK1) was reported as an angiogenic factor, which is associated with tumor progression, cell invasion, and metastasis in colorectal cancer. Although the association between PROK1 expression in primary cancer lesion and patient prognosis was reported, it is unclear whether plasma PROK1 concentration may be a predictive factor in colorectal cancer patients. This study investigated the association between PROK1 concentration in plasma and prognosis in colorectal cancer patients. Methods: We measured preoperative PROK1 plasma levels using ELISA method, while PROK1 expression in primary cancer lesion was evaluated using immunohistochemistry (IHC). The association between plasma PROK1 levels and cancer-related survival rate (CRS) was evaluated. Additionally, we examined whether simultaneous PROK1 expression in both primary cancer lesions and plasma was correlated with CRS. The cancer-related survival rate was calculated using the Kaplan-Meier method, and survival estimates were compared using the log-rank test. Results: We have gathered eligible 130 CRC patients retrospectively. Out of 130 patients, 61 (46.9%) were positive on IHC in primary cancer, and 69 (53.1%) were negative, while 43 (33.1%) had high-value PROK1 in plasma. Out of these 43, 30 (25.4%) also had concomitant higher IHC expression in primary cancer. The plasma PROK1 levels tended to increase with advancing stages. The plasma PROK1-positive group had a lower 5-year CRS than the negative group (63.6% vs. 88.2%; P = 0.006). Additionally, simultaneous PROK1 expression was associated with a more significant decrease of 5-year CRS than both negative groups in all stages (76.2% vs. 92.5%; P = 0.003) and stage III (59.3% vs. 84.5%; P = 0.047). Multivariate analysis showed simultaneous PROK1 expression was independently associated with worse CRS (HR, 1.97; 95% CI 1.20‑3.24, P < 0.01). Conclusion: PROK1 expression in preoperative plasma reflects poor prognosis in patients undergoing curative resection for colorectal cancer. The plasma PROK1 level may be a potential predictive marker, especially in stage III colorectal cancer patients.