Miller Hannah, Czigany Zoltan, Lurje Isabella, Reichelt Sophie, Bednarsch Jan, Strnad Pavel, Trautwein Christian, Roderburg Christoph, Tacke Frank, Gaisa Nadine Therese, Knüchel-Clarke Ruth, Neumann Ulf Peter, Lurje Georg
Charité-Universitätsmedizin Berlin, Department of Surgery, Campus Charité Mitte|Campus Virchow-Klinikum, 13353 Berlin, Germany.
Department of Surgery and Transplantation, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany.
Cancers (Basel). 2020 Dec 18;12(12):3826. doi: 10.3390/cancers12123826.
Tumor angiogenesis plays a pivotal role in hepatocellular carcinoma (HCC) biology. Identifying molecular prognostic markers is critical to further improve treatment selection in these patients. The present study analyzed a subset of 10 germline polymorphisms involved in tumor angiogenesis pathways and their impact on prognosis in HCC patients undergoing partial hepatectomy in a curative intent. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 127 HCC patients at a German primary care hospital. Genomic DNA was extracted, and genotyping was carried out using polymerase chain reaction (PCR)-restriction fragment length polymorphism-based protocols. Polymorphisms in interleukin-8 (IL-8) (rs4073; = 0.047, log-rank test) and vascular endothelial growth factor (VEGF C + 936T) (rs3025039; = 0.045, log-rank test) were significantly associated with disease-free survival (DFS). After adjusting for covariates in the multivariable model, IL-8 T-251A (rs4073) (adjusted = 0.010) and a combination of "high-expression" variants of rs4073 and rs3025039 (adjusted = 0.034) remained significantly associated with DFS. High-expression variants of IL-8 T-251A may serve as an independent molecular marker of prognosis in patients undergoing surgical resection for HCC. Assessment of the patients' individual genetic risks may help to identify patient subgroups at high risk for recurrence following curative-intent surgery.
肿瘤血管生成在肝细胞癌（HCC）生物学中起着关键作用。识别分子预后标志物对于进一步改善这些患者的治疗选择至关重要。本研究分析了10个参与肿瘤血管生成途径的种系多态性子集及其对接受根治性部分肝切除术的HCC患者预后的影响。从德国一家初级保健医院的127例HCC患者中获取福尔马林固定石蜡包埋（FFPE）组织。提取基因组DNA，并使用基于聚合酶链反应（PCR）-限制性片段长度多态性的方案进行基因分型。白细胞介素-8（IL-8）（rs4073；P = 0.047，对数秩检验）和血管内皮生长因子（VEGF C + 936T）（rs3025039；P = 0.045，对数秩检验）中的多态性与无病生存期（DFS）显著相关。在多变量模型中调整协变量后，IL-8 T-251A（rs4073）（调整后P = 0.010）以及rs4073和rs3025039的“高表达”变体组合（调整后P = 0.034）仍与DFS显著相关。IL-8 T-251A的高表达变体可能作为接受HCC手术切除患者预后的独立分子标志物。评估患者的个体遗传风险可能有助于识别根治性手术后复发风险高的患者亚组。
