Medical Oncology Unit, Macerata General Hospital, ASUR Marche AV3, Macerata, Italy.
Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy.
Target Oncol. 2020 Feb;15(1):115-126. doi: 10.1007/s11523-020-00698-x.
Sorafenib represents one of the therapeutic strongholds for advanced hepatocellular carcinoma (HCC), but unfortunately, predictive factors are lacking. We previously reported that the VEGF single nucleotide polymorphisms (SNPs) rs2010963 and rs4604006 might correlate with clinical outcomes in sorafenib-treated HCC patients.
The objective of the ALICE-2 study is to define a prognostic angiogenesis profile to better identify HCC patients who are more likely to benefit from sorafenib treatment.
From 2008 to 2015, all consecutive HCC patients receiving sorafenib according to the Italian label were tested for specific HIF-1α, VEGF, and VEGFR SNPs. Results from angiogenesis genotyping were then correlated with clinical outcome parameters.
Globally, a total of 210 patients were enrolled. At multivariate analysis rs12434438 of HIF1α, rs2010963 of VEGF-A, and rs4604006 of VEGF-C were confirmed as independent predictive factors. At the combined analysis of significant SNPs, the presence of two favourable alleles of rs2010963 and rs4604006 of VEGF compared to only one or to none favourable alleles, was able to identify three separate patients populations with different time-to-progression (TTP) (10.8 vs. 5.6 vs. 3.7 months, respectively; p < 0.0001) and overall survival (OS) (19.0 vs. 13.5 vs. 7.5 months, respectively; p < 0.0001). Furthermore, the presence of the GG genotype of rs12434438 (HIF-1α) seemed able to select a population with a particularly poor outcome, independently from the clinical effect of the two VEGF SNPs (TTP: 2.6 months, HR: 0.54, p = 0.0374; OS: 6.6 months, p = 0.0061, HR: 0.43).
Our findings show that polymorphism analysis of HIF-1α, VEGF, and VEGFR genes may represent a prognostic panel to better identify HCC patients who are more likely to benefit from sorafenib treatment.
索拉非尼是治疗晚期肝细胞癌（HCC）的主要药物之一，但目前缺乏有效的预测因子。我们之前的研究发现，VEGF 单核苷酸多态性（SNP）rs2010963 和 rs4604006 可能与接受索拉非尼治疗的 HCC 患者的临床结局相关。
ALICE-2 研究旨在确定一种预测血管生成的方法，以更好地识别更有可能从索拉非尼治疗中获益的 HCC 患者。
2008 年至 2015 年，所有根据意大利标签接受索拉非尼治疗的 HCC 患者均接受了特定的 HIF-1α、VEGF 和 VEGFR SNP 检测。随后将血管生成基因分型结果与临床结局参数相关联。
全球共纳入 210 例患者。多变量分析证实 HIF1α 的 rs12434438、VEGF-A 的 rs2010963 和 VEGF-C 的 rs4604006 为独立预测因子。在对有意义的 SNP 的联合分析中，与只有一个或没有有利等位基因相比，VEGF 的 rs2010963 和 rs4604006 两个有利等位基因的存在可将患者分为三组，具有不同的无进展生存期（TTP）（10.8 个月、5.6 个月和 3.7 个月，p<0.0001）和总生存期（OS）（19.0 个月、13.5 个月和 7.5 个月，p<0.0001）。此外，HIF-1α 的 rs12434438（GG 基因型）的存在似乎能够选择一组临床效果较差的患者，而与两个 VEGF SNP 的临床效果无关（TTP：2.6 个月，HR：0.54，p=0.0374；OS：6.6 个月，p=0.0061，HR：0.43）。
我们的研究结果表明，HIF-1α、VEGF 和 VEGFR 基因的多态性分析可能是一种预测模型，可更好地识别更有可能从索拉非尼治疗中获益的 HCC 患者。
