腫瘤CXCR4表現與胰臟癌術後存活之關係:回溯性世代研究

Abstract

背景：胰臟癌病患接受腫瘤切除手術後有60％會發生肝臟復發，其預後極差。實驗性研究顯示趨化素受器CXCR4為胰臟癌病患手術後肝臟轉移之重要因子，然而其與病患預後之關連未曾獲得證實。本研究目的在探討CXCR4之表現與胰臟癌術後無肝臟復發存活及總存活之關連。 方法：共有97位接受腫瘤切除手術之患者被納入研究。利用免疫組織染色測定CXCR4之表現，然後以Kaplan-Meier estimate及多變數proportional hazards 模型分析CXCR4表現與無肝臟復發存活及總存活之關係。 結果：腫瘤CXCR4陽性之病患其預後較CXCR4陰性者為差，其無肝臟復發存活 （中位數8.7 vs 39.7個月，p＝0.004）及總存活（中位數10.2 vs 22.3個月，p<0.001）較短。CXCR4陽性之IIa期病患其總存活與IIb期者相近，較CXCR4陰性之IIa期患者顯著較短（p＝0.002）。CXCR4陽性對於肝臟復發與因胰臟癌死亡之校正危險比分別為2.22（p＝0.018）及1.78（p＝0.041）。 結論：胰臟癌表現CXCR4為術後肝臟復發與死亡之獨立預後因子。CXCR4免疫組織染色可以提供其他已知之預後預測因子所無法提供之資訊，且可改善TNM分期對術後存活之預測。

ABSTRACT Purpose: Liver recurrence develops in 60% of patients who undergo resection for pancreatic cancer (PC) and predicts a dismal prognosis. Experimental evidences suggested chemokine receptor CXCR4 as the key mediator of liver metastasis in PC, but its significance has not been investigated with patient outcome. This study aimed to investigate the potential associations between CXCR4 expression and liver recurrence or overall survival after resection for PC. Methods: Ninety-seven patients undergoing R0 resection were evaluated. CXCR4 expression was analyzed by immunohistochemistry, and its association with liver recurrence-free or overall survival was analyzed by Kaplan-Meier estimates and multivariable proportional hazards models. Results: Patients with CXCR4-positive tumors had worse prognosis than those with CXCR4-negative tumors, with a shorter liver recurrence-free survival (median: 8.7 vs. 39.7 months; p=0.004) and overall survival (median: 10.2 vs. 22.3 months; p<0.001). Overall survival for CXCR4-positive stage IIa patients was similar to stage IIb patients and significantly shorter than CXCR4-negative stage IIa patients (p=0.002). The adjusted hazard ratio of positive CXCR4 immunostaining was 2.22 for liver recurrence (p=0.018), and 1.78 for death due to PC (p=0.041), respectively. Conclusion: CXCR4 expression is an independent predictor of early liver recurrence and death after resection for PC. CXCR4 immunohistochemistry provides exclusive prognostic information that can not be replaced by known prognostic factors and supplements TNM stage in predicting survival.