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 (p≤ 0.001). In multivariate analysis, absence of active autophagy (HR = 2, 95% CI = 1.1–3.5,p= 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 (p= 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）中影响的数据仍然匮乏。因此，本研究探讨了活跃自噬的作用及其对CCA患者生存的影响。我们评估了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。通过免疫组织化学检测自噬关键蛋白。对用于免疫耗竭基因集表达谱分析的肝内胆管癌（iCCA）样本进行了自噬相关基因的计算机模拟分析。在172例CCA患者中，23.3%存在活跃自噬。Kaplan-Meier曲线显示，活跃自噬组与非活跃自噬组的中位总生存期分别为68.4个月（95% CI = 46.9–89.9个月）和32.7个月（95% CI = 23.6–41.8个月）（p≤0.001）。多变量分析表明，缺乏活跃自噬（HR = 2，95% CI = 1.1–3.5，p=0.015）是总生存期的独立风险因素。差异表达谱分析显示，非活跃自噬患者的组蛋白去乙酰化酶（HDAC）mRNA显著上调。与此一致，泛乙酰化赖氨酸在持续自噬的CCA患者中显著更突出（p=0.005）。我们的研究结果强化了活跃自噬作为预后相关标志物和潜在治疗靶点的重要性。
肿瘤(癌症)患者之家