Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer /Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer /Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
BMC Cancer. 2019 Mar 8;19(1):213. doi: 10.1186/s12885-019-5429-3.
Although surgical resection provides a cure for patients with intrahepatic cholangiocarcinoma (ICC), the risk of mortality and recurrence remains high. Several biomarkers are reported to be associated with the prognosis of ICC, including Beclin-1, ARID1A, carbonic anhydrase IX (CA9) and isocitrate dehydrogenase 1 (IDH1), but results are inconsistent. Therefore, a histopathological retrospective study was performed to simultaneously investigate the relationship of these four potential biomarkers with clinicopathological parameters and their prognostic values in patients with ICC.
A total of 113 patients with ICC were enrolled from Cancer Hospital of Chinese Academy of Medical Sciences between January 1999 and June 2015. The expression of Beclin-1, ARID1A, IDH1 and CA9 were determined by immunohistochemical staining. The prognostic values of the four biomarkers were analyzed by Cox regression and the Kaplan-Meier method.
Beclin-1, ARID1A, CA9 and IDH1 were highly expressed in ICC tumor tissues. Higher mortality was positively associated with Beclin-1 expression (HR = 2.39, 95% CI = 1.09-5.24) and higher recurrence was positively associated with ARID1A expression (HR = 1.71, 95% CI = 1.06-2.78). Neither CA9 nor IDH1 expression was significantly associated with mortality or disease recurrence. Kaplan-Meier survival curves showed that ICC patients with higher Beclin-1 and ARID1A expression had a lower survival rate and a worse recurrence rate than patients with low Beclin-1 and ARID1A expression (p < 0.05).
High Beclin-1 and ARIDIA expression are strongly associated with poor prognosis in ICC patients, and thus Beclin-1 and ARID1A should be simultaneously considered as potential prognostic biomarkers for ICC patients.
尽管手术切除为肝内胆管癌(ICC)患者提供了治愈的机会,但死亡率和复发率仍然很高。有报道称,几种生物标志物与 ICC 的预后相关,包括 Beclin-1、ARID1A、碳酸酐酶 IX(CA9)和异柠檬酸脱氢酶 1(IDH1),但结果不一致。因此,进行了一项组织病理学回顾性研究,同时调查这四种潜在生物标志物与 ICC 患者临床病理参数的关系及其预后价值。
本研究共纳入 1999 年 1 月至 2015 年 6 月期间在中国医学科学院肿瘤医院就诊的 113 例 ICC 患者。采用免疫组织化学染色法检测 Beclin-1、ARID1A、IDH1 和 CA9 的表达。采用 Cox 回归和 Kaplan-Meier 法分析四种生物标志物的预后价值。
Beclin-1、ARID1A、CA9 和 IDH1 在 ICC 肿瘤组织中高表达。较高的死亡率与 Beclin-1 表达呈正相关(HR=2.39,95%CI=1.09-5.24),较高的复发率与 ARID1A 表达呈正相关(HR=1.71,95%CI=1.06-2.78)。CA9 和 IDH1 表达与死亡率或疾病复发均无显著相关性。Kaplan-Meier 生存曲线显示,Beclin-1 和 ARID1A 高表达的 ICC 患者的生存率和复发率均低于 Beclin-1 和 ARID1A 低表达的患者(p<0.05)。
Beclin-1 和 ARIDIA 高表达与 ICC 患者的不良预后密切相关,因此 Beclin-1 和 ARID1A 可同时作为 ICC 患者潜在的预后生物标志物。