Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Pancreatology. 2024 Nov;24(7):1021-1030. doi: 10.1016/j.pan.2024.10.001. Epub 2024 Oct 1.
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).
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 vs. cCav1) or cancer-associated fibroblasts (fCav1 vs. fCav1).
Among all 615 patients, 40.7% were cCav1 and 72.7% were fCav1. cCav1 was associated with worse overall survival (OS) (p = 0.001) and recurrence-free survival (RFS) (p = 0.001) than cCav1, 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 patients with NAC showed better OS than those without, while there was no significant difference between cCav1 patients with NAC and those without. cCav1 was associated with early recurrence (< 6 months) and liver metastasis after resection. Multivariate analysis revealed cCav1 as an independent predictor of liver metastasis.
cCav1 correlated with worse survival, early recurrence, and liver metastasis after resection for PDAC, while NAC improved survival in cCav1 patients. The Evaluation of cCav1 status could provide additional information contributing to the personalized management of PDAC.
背景/目的：在癌细胞（cCav1）或癌相关成纤维细胞（fCav1）中表达的窖蛋白-1（Cav1），根据癌症类型或癌症阶段，发挥促癌或抑癌作用。我们旨在阐明 cCav1 或 fCav1 对接受根治性切除术的胰腺导管腺癌（PDAC）患者的生存、复发模式和新辅助化疗（NAC）疗效的影响。
构建了包含 615 例接受 PDAC 根治性切除术患者的组织微阵列。通过免疫组织化学评估 Cav1 表达。根据癌细胞（cCav1 与 cCav1）或癌相关成纤维细胞（fCav1 与 fCav1）中 Cav1 的表达，将患者分为两组。
在所有 615 例患者中，40.7%为 cCav1，72.7%为 fCav1。cCav1 与总体生存（OS）（p=0.001）和无复发生存（RFS）（p=0.001）较差相关，并且是 OS 和 RFS 多变量分析的独立预后因素（OS：p=0.001，风险比[HR] 1.361；RFS：p=0.001，HR 1.348）。在 596 例可切除/边界可切除 PDAC 患者中，接受 NAC 的 cCav1 患者的 OS 优于未接受 NAC 的患者，而接受 NAC 的 cCav1 患者与未接受 NAC 的患者之间无显著差异。cCav1 与 PDAC 切除后早期复发（<6 个月）和肝转移相关。多变量分析显示 cCav1 是肝转移的独立预测因子。
cCav1 与 PDAC 患者的生存较差、早期复发和肝转移相关，而 NAC 可改善 cCav1 患者的生存。cCav1 状态的评估可为 PDAC 的个体化治疗提供附加信息。
