Background/Aim: Biliary tract cancer (BTC) has a poor prognosis due to its highly invasive and metastatic potential. Ataxia-telangiectasia mutated (ATM) is a key regulator of DNA damage response and an emerging therapeutic target; however, the association between the expression of ATM and the prognosis in advanced BTC is unknown. We aimed to identify the relationship between ATM expression, clinicopathological characteristics, and survival outcomes in patients with advanced BTC. Patients and Methods: We analyzed 113 patients with advanced BTC who received first-line gemcitabine and platinum. Results: The tumor location was intrahepatic cholangiocarcinoma (IH-CCC) in 43 patients, extrahepatic cholangiocarcinoma (EH-CCC) in 49, and gallbladder (GB) cancer in 21 patients. Fifty-four patients (47.8%) exhibited loss of ATM protein expression. The overall response rate (ORR) of ATM loss and intact ATM was 13.3% and 19.6%, respectively. In a subgroup analysis, EH-CCC patients with ATM loss tended to have improved PFS after platinum-based chemotherapy compared to those with intact ATM (7.9 vs. 6.2 months, respectively; p=0.050). Conclusion: We demonstrated that ATM loss could be a prognostic marker after platinum-based chemotherapy in patients with advanced EH-CCC.

中文翻译：

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ATM 表达作为一线吉西他滨和铂类化疗治疗晚期胆道癌患者的预后标志物

背景/目的：胆道癌 (BTC) 由于具有高度侵袭性和转移性，因此预后较差。共济失调毛细血管扩张突变 (ATM) 是 DNA 损伤反应的关键调节因子和新兴的治疗靶点；然而，ATM 的表达与晚期 BTC 预后之间的关联尚不清楚。我们旨在确定晚期 BTC 患者的 ATM 表达、临床病理特征和生存结果之间的关系。患者和方法：我们分析了 113 名接受一线吉西他滨和铂类治疗的晚期 BTC 患者。结果：肿瘤部位为肝内胆管癌（IH-CCC）43例，肝外胆管癌（EH-CCC）49例，胆囊癌（GB）21例。54 名患者 (47.8%) 表现出 ATM 蛋白表达的丧失。ATM 丢失和完整 ATM 的总体响应率 (ORR) 分别为 13.3% 和 19.6%。在亚组分析中，与具有完整 ATM 的患者相比，具有 ATM 缺失的 EH-CCC 患者在接受铂类化疗后的 PFS 往往有所改善（分别为 7.9 个月和 6.2 个月；p=0.050）。结论：我们证明 ATM 丢失可能是晚期 EH-CCC 患者铂类化疗后的预后标志物。