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

• Published in: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2024-11, Vol.24 (7), p.1021-1030
• Main Authors: Hirose, Yuki, Oba, Atsushi, Takamatsu, Manabu, Hamada, Tsuyoshi, Takeda, Tsuyoshi, Suzuki, Tatsunori, Maekawa, Aya, Kitano, Yuki, Sato, Shoki, Kobayashi, Kosuke, Omiya, Kojiro, Ono, Yoshihiro, Sato, Takafumi, Ito, Hiromichi, Sasaki, Takashi, Ozaka, Masato, Takeuchi, Kengo, Sasahira, Naoki, Inoue, Yosuke, Wakai, Toshifumi, Takahashi, Yu
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - metabolism; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Pancreatic Ductal - surgery; Caveolin 1 - genetics; Caveolin 1 - metabolism; Caveolin-1; Chemo-resistance; Female; Humans; Liver metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Pancreatic ductal adenocarcinoma; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - surgery; Prognosis; Survival; Survival Analysis
• ISSN: 1424-3903; 1424-3911; 1424-3911
• DOI: 10.1016/j.pan.2024.10.001

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). 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 (cCav1high vs. cCav1low) or cancer-associated fibroblasts (fCav1high vs. fCav1low). Among all 615 patients, 40.7% were cCav1high and 72.7% were fCav1high. cCav1high was associated with worse overall survival (OS) (p = 0.001) and recurrence-free survival (RFS) (p = 0.001) than cCav1low, 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, cCav1high patients with NAC showed better OS than those without, while there was no significant difference between cCav1low patients with NAC and those without. cCav1high was associated with early recurrence (< 6 months) and liver metastasis after resection. Multivariate analysis revealed cCav1high as an independent predictor of liver metastasis. cCav1high correlated with worse survival, early recurrence, and liver metastasis after resection for PDAC, while NAC improved survival in cCav1high patients. The Evaluation of cCav1 status could provide additional information contributing to the personalized management of PDAC.