Lurje Isabella, Czigany Zoltan, Bednarsch Jan, Gaisa Nadine Therese, Dahl Edgar, Knüchel Ruth, Miller Hannah, Ulmer Tom Florian, Strnad Pavel, Trautwein Christian, Tacke Frank, Neumann Ulf Peter, Lurje Georg
Department of Hepatology and Gastroenterology, Campus Charité Mitte, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
Liver Cancer. 2022 Jan 25;11(2):162-173. doi: 10.1159/000521613. eCollection 2022 Apr.
Perihilar cholangiocarcinoma (pCCA) is a rare primary liver malignancy. Even in patients amenable to surgery, outcomes are often dismal. Here, we aimed to identify prognostic markers for patient outcomes by analyzing functionally relevant single-nucleotide polymorphisms (SNPs) in genes with a role in tumor inflammation and angiogenesis. We analyzed 11 polymorphisms in the inflammation-angiogenesis axis (, and genes) for their prediction of tumor recurrence and survival in pCCA patients undergoing surgery in a curative intent.
Samples were obtained from 111 patients with pCCA undergoing liver resection in curative intent. DNA was extracted and analyzed using polymerase chain reaction-restriction fragment length polymorphism protocols and correlated with patients' outcomes.
Out of the assessed variants, only the (also: interleukin-8-receptor alpha - ) +860C>G heterozygous polymorphism (rs2234671) was associated with decreased disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) (18/111 (16.2%), median DFS 14 months, log-rank = 0.007; median CSS 31 months, log-rank = 0.007; and median OS 6 months, log-rank = 0.002), compared to the GG genotype (92/111 (82.9%), median DFS 55 months, median CSS 63 months, and median OS 33 months). In the multivariate analysis, +860C>G remained an independent prognostic factor for DFS (adjusted = 0.008), CSS (adjusted = 0.001), and OS (adjusted = 0.001).
Genetic variant of +860C>G may serve as a molecular marker for DFS, CSS, and OS in patients undergoing curative-intent surgery for pCCA, indicating that the analysis of SNPs in genes involved in immune-mediated angiogenesis may help to identify patient subgroups at high risk for dismal oncological and overall outcome.
肝门部胆管癌（pCCA）是一种罕见的原发性肝脏恶性肿瘤。即使是适合手术的患者，预后往往也很差。在此，我们旨在通过分析在肿瘤炎症和血管生成中起作用的基因中功能相关的单核苷酸多态性（SNP）来确定患者预后的预测标志物。我们分析了炎症 - 血管生成轴（、和基因）中的11个多态性，以预测接受根治性手术的pCCA患者的肿瘤复发和生存情况。
从111例接受根治性肝切除术的pCCA患者中获取样本。提取DNA并使用聚合酶链反应 - 限制性片段长度多态性方案进行分析，并与患者的预后相关联。
在评估的变异中，只有（也称为白细胞介素 - 8受体α - ）+860C>G杂合多态性（rs2234671）与无病生存期（DFS）、癌症特异性生存期（CSS）和总生存期（OS）降低相关（111例中的18例（16.2%），中位DFS为14个月，对数秩检验=0.007；中位CSS为31个月，对数秩检验=0.007；中位OS为6个月，对数秩检验=0.002），而GG基因型患者（111例中的92例（82.9%），中位DFS为55个月，中位CSS为63个月，中位OS为33个月）则不然。在多变量分析中，+860C>G仍然是DFS（调整后=0.008）、CSS（调整后=0.001）和OS（调整后=0.001）的独立预后因素。
+860C>G的基因变异可能作为接受pCCA根治性手术患者DFS、CSS和OS的分子标志物，表明分析参与免疫介导血管生成的基因中的SNP可能有助于识别肿瘤学和总体预后较差的高危患者亚组。
