Caveolin-1 expression is a predictor of survival and recurrence patterns in resected pancreatic ductal adenocarcinoma

Abstract

Background/objective: Caveolin-1 (Cav1) expressed in cancer cells (cCav1) or cancer-associated fibroblasts (fCav1) exerts either pro- or anti-tumorigenic effects depending on the cancer type or stage of cancer. We aimed to clarify the impact of cCav1 or fCav1 on survival, recurrence patterns, and efficacy of neoadjuvant chemotherapy (NAC) in resected pancreatic ductal adenocarcinoma (PDAC).

Methods: Tissue microarrays were constructed including 615 patients who underwent curative resection for PDAC. Cav1 expression was evaluated by immunohistochemistry. Patients were divided into two groups based on Cav1 expression in cancer cells (cCav1_high vs. cCav1_low) or cancer-associated fibroblasts (fCav1_high vs. fCav1_low).

Results: Among all 615 patients, 40.7% were cCav1_high and 72.7% were fCav1_high. cCav1_high was associated with worse overall survival (OS) (p = 0.001) and recurrence-free survival (RFS) (p = 0.001) than cCav1_low, and was an independent prognostic factor in multivariate analysis of OS and RFS (OS: p = 0.001, hazard ratio [HR] 1.361; RFS: p = 0.001, HR 1.348). Among 596 patients with resectable/borderline resectable PDAC, cCav1_high patients with NAC showed better OS than those without, while there was no significant difference between cCav1_low patients with NAC and those without. cCav1_high was associated with early recurrence (< 6 months) and liver metastasis after resection. Multivariate analysis revealed cCav1_high as an independent predictor of liver metastasis.

Conclusions: cCav1_high correlated with worse survival, early recurrence, and liver metastasis after resection for PDAC, while NAC improved survival in cCav1_high patients. The Evaluation of cCav1 status could provide additional information contributing to the personalized management of PDAC.

Keywords: Caveolin-1; Chemo-resistance; Liver metastasis; Pancreatic ductal adenocarcinoma; Survival.