Cholangiocarcinoma (CCA), the second most common primary liver tumor, is associated with a dismal outcome, and useful prognostic markers are not currently available in clinical practice. SerpinB3, a serine protease inhibitor, was recently found to play a relevant role in malignant transformation in different cancers. The aim of the present study was to determine the expression of SerpinB3/4 in tissue and serum samples of patients with CCA in relation to clinical outcomes. SerpinB3/4 was assessed in the tissue microarrays (TMAs) of 123 surgically resected CCAs. ELISA assays were carried out in 188 patients with CCA to detect the free and IgM-linked forms of SerpinB3/4. Overall survival was analyzed in relation to SerpinB3/4 expression, and Cox models were used to identify the variables associated with survival. High levels of SerpinB3/4 (TMA score 2+/3+) were detected in 15 tumors (12.2%), characterized by a more advanced TNM stage (III/IV: 64.3% vs. 31.3%;p= 0.031) and lower overall patient survival, independently of CCA subclass (intrahepatic CCA: median 1.1 (0.8—Not Estimable, NE) vs. 2.4 (1.8–3.4) years;p= 0.0007; extrahepatic CCA: median 0.8 (0.2—NE) vs. 2.2 (1.5–5.4) years;p= 0.011). Vascular invasion (p= 0.027) and SerpinB3/4 scores (p= 0.0016) were independently associated with mortality in multivariate analysis. Patients who had detectable free or IgM-linked SerpinB3/4 in their serum showed poorer survival (1 vs. 2.4 years,p= 0.015, for free SerpinB3/4, and 1 vs. 2.6 years,p= 0.0026, for SerpinB3/4–IgM). In conclusion, high levels of SerpinB3/4 in tissue and serum in CCA are associated with poor outcomes after surgery, regardless of tumor subclass.
胆管癌（CCA）作为第二常见的原发性肝脏肿瘤，其预后极差，目前临床实践中尚缺乏有效的预后标志物。丝氨酸蛋白酶抑制剂SerpinB3近期被发现与多种癌症的恶性转化过程密切相关。本研究旨在探讨CCA患者组织及血清样本中SerpinB3/4的表达水平与临床预后的关联性。研究对123例手术切除的CCA组织芯片（TMAs）进行SerpinB3/4检测，并采用ELISA法对188例CCA患者血清中游离型及IgM结合型SerpinB3/4进行定量分析。通过生存分析评估SerpinB3/4表达与总生存期的关系，并采用Cox模型筛选与生存相关的变量。结果显示，15例肿瘤（12.2%）呈现SerpinB3/4高表达（TMA评分2+/3+），这些病例具有更晚期的TNM分期（III/IV期：64.3% vs. 31.3%；p=0.031）和更短的总生存期，且该关联独立于CCA亚型（肝内CCA：中位生存期1.1年（0.8-不可估计）vs. 2.4年（1.8-3.4），p=0.0007；肝外CCA：中位生存期0.8年（0.2-不可估计）vs. 2.2年（1.5-5.4），p=0.011）。多因素分析显示血管侵犯（p=0.027）和SerpinB3/4评分（p=0.0016）是影响死亡率的独立危险因素。血清中检出游离型或IgM结合型SerpinB3/4的患者生存期显著缩短（游离型：1年 vs. 2.4年，p=0.015；IgM结合型：1年 vs. 2.6年，p=0.0026）。综上所述，无论CCA亚型如何，组织及血清中高水平的SerpinB3/4均与术后不良预后密切相关。
SerpinB3/4 Expression Is Associated with Poor Prognosis in Patients with Cholangiocarcinoma
肿瘤(癌症)患者之家