Kurowski Konrad, Föll Melanie, Werner Tilman, Schilling Oliver, Werner Martin, Fichtner-Feigl Stefan, Bengsch Bertram, Bronsert Peter, Holzner Philipp Anton, Timme Sylvia
Institute for Surgical Pathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
Core Facility Histopathology and Digital Pathology Freiburg, Medical Center - University of Freiburg, Germany.
J Cancer. 2025 Jan 1;16(1):1-11. doi: 10.7150/jca.99944. eCollection 2025.
Intrahepatic cholangiocarcinoma (iCC) is a rare malignant liver tumor with limited therapeutic advancements. Despite its increasing global incidence knowledge of treatment options remains stagnant, leading to poor five-year patient survival rates and high recurrence post-surgery. ALDH1A1, a member of the ALDH superfamily, is associated with cancer stem cells and has conflicting reports regarding its prognostic role in iCC. This retrospective study analyzed 69 iCC patient samples from University Hospital Freiburg. Tissue microarrays (TMAs) were constructed, and ALDH1A1 expression was immunohistochemically assessed using machine learning algorithms. Script-based Survival analysis employed Kaplan-Meier curves, log-rank tests, and Cox Proportional Hazards Models. ALDH1A1 overexpression, both in tumor and stromal cells, correlates with favorable overall survival in iCC. Gender-specific analyses indicate a more pronounced effect in females. These findings suggest ALDH1A1 as a potential prognostic biomarker in iCC, warranting further validation in larger cohorts and exploration as a therapeutic target.
肝内胆管癌（iCC）是一种罕见的恶性肝脏肿瘤，治疗进展有限。尽管其全球发病率不断上升，但治疗选择的相关知识仍停滞不前，导致患者五年生存率低且术后复发率高。醛脱氢酶1A1（ALDH1A1）是ALDH超家族的成员，与癌症干细胞相关，关于其在iCC中的预后作用的报道存在矛盾。这项回顾性研究分析了来自弗莱堡大学医院的69例iCC患者样本。构建了组织微阵列（TMA），并使用机器学习算法通过免疫组织化学评估ALDH1A1的表达。基于脚本的生存分析采用了Kaplan-Meier曲线、对数秩检验和Cox比例风险模型。肿瘤细胞和基质细胞中ALDH1A1的过表达均与iCC患者较好的总生存期相关。性别特异性分析表明，该效应在女性中更为明显。这些发现表明ALDH1A1可能是iCC的一种预后生物标志物，值得在更大的队列中进一步验证，并作为治疗靶点进行探索。
