Bankov Katrin, Schulze Falko, Gretser Steffen, Reis Henning, Abedin Nada, Finkelmeier Fabian, Trojan Jörg, Zeuzem Stefan, Schnitzbauer Andreas A, Walter Dirk, Wild Peter J, Kinzler Maximilian N
Dr. Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany.
Department of Internal Medicine I, University Hospital Frankfurt, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany.
Cancers (Basel). 2023 Aug 29;15(17):4322. doi: 10.3390/cancers15174322.
Data on the impact of autophagy in primary cholangiocarcinoma (CCA) remain scarce. Here, we therefore investigated the role of active autophagy and its impact on survival in CCA patients. All CCA patients who underwent surgical resection with curative intent between 08/2005 and 12/2021 at University Hospital Frankfurt were evaluated. Autophagic key proteins were studied by immunohistochemistry. iCCA processed for gene expression profiling of immune-exhaustion gene sets was used for an autophagy approach in silico. Active autophagy was present in 23.3% of the 172 CCA patients. Kaplan-Meier curves revealed median OS of 68.4 months (95% CI = 46.9-89.9 months) and 32.7 months (95% CI = 23.6-41.8 months) for active and non-active autophagy, respectively ( ≤ 0.001). In multivariate analysis, absence of active autophagy (HR = 2, 95% CI = 1.1-3.5, = 0.015) was an independent risk factor for OS. Differential-expression profiling revealed significantly upregulated histone deacetylases (HDAC) mRNA in patients showing non-active autophagy. In line with this, pan-acetylated lysine was significantly more prominent in CCA patients with ongoing autophagy ( = 0.005). Our findings strengthen the role of active autophagy as a prognostically relevant marker and a potential therapeutic target.
关于自噬在原发性胆管癌（CCA）中的影响的数据仍然匮乏。因此，我们在此研究了活跃自噬的作用及其对CCA患者生存的影响。对2005年8月至2021年12月期间在法兰克福大学医院接受根治性手术切除的所有CCA患者进行了评估。通过免疫组织化学研究自噬关键蛋白。对经过免疫耗竭基因集基因表达谱分析的肝内胆管癌（iCCA）进行了计算机模拟自噬研究。172例CCA患者中，23.3%存在活跃自噬。Kaplan-Meier曲线显示，活跃自噬和非活跃自噬患者的中位总生存期（OS）分别为68.4个月（95%置信区间=46.9-89.9个月）和32.7个月（95%置信区间=23.6-41.8个月）（P≤0.001）。在多变量分析中，无活跃自噬（风险比=2，95%置信区间=1.1-3.5，P=0.015）是OS的独立危险因素。差异表达谱分析显示，在表现为非活跃自噬的患者中，组蛋白去乙酰化酶（HDAC）mRNA显著上调。与此一致的是，在持续自噬的CCA患者中，泛乙酰化赖氨酸显著更突出（P=0.005）。我们的研究结果强化了活跃自噬作为一个具有预后相关性的标志物和潜在治疗靶点的作用。
