Department of Health Sciences, Health Sciences Faculty, European University of Madrid, Villaviciosa de Odón, 28670 Madrid, Spain.
Department of Medicine, Health Sciences Faculty, Universidad Europea de Madrid, Villaviciosa de Odón, 28670 Madrid, Spain.
Int J Mol Sci. 2021 Jan 30;22(3):1381. doi: 10.3390/ijms22031381.
Angiogenesis pathway genes show substantial genetic variability causing inter-individual differences in responses to anti-angiogenic drugs. We examined 20 single nucleotide polymorphisms (SNPs) in 13 of these genes to predict tumour response and clinical outcome measured as progression free survival (PFS) and overall survival (OS) in 57 patients with metastatic colorectal cancer (mCRC) given bevacizumab plus chemotherapy. SNPs were detected (iPLEX® Assay) in genomic DNA extracted from formalin-fixed paraffin-embedded tumour specimens. The variant allele rs11188513 was associated with a good tumour response ( = 0.024). Patients homozygous for the wild-type allele rs1960669 showed a median PFS of 10.95 months versus 5.44 months for those with at least one variant allele-A (HR 3.30; 95% CI: 1.52-7.14; = 0.001). Patients homozygous for wild-type rs2236416 and rs2274755 showed a median PFS of 9.48 months versus 6 and 6.62 months, respectively, for those with at least one variant allele ( = 0.022, = 0.043, respectively). OS was also lengthened to 30.92 months ( = 0.034) in carriers of wild-type rs2445365 versus 22.07 months for those carrying at least one variant allele-A. These gene variants were able to predict clinical outcome and tumour response in mCRC patients given bevacizumab-based therapy.
血管生成途径基因存在显著的遗传变异性，导致个体对抗血管生成药物反应的差异。我们检测了这 13 个基因中的 20 个单核苷酸多态性（SNP），以预测 57 例转移性结直肠癌（mCRC）患者接受贝伐单抗联合化疗的肿瘤反应和临床结果，这些结果以无进展生存期（PFS）和总生存期（OS）来衡量。SNP 是从福尔马林固定石蜡包埋的肿瘤标本中提取的基因组 DNA 中检测到的（iPLEX®assay）。变体等位基因 rs11188513 与良好的肿瘤反应相关（=0.024）。野生型等位基因 rs1960669 纯合子患者的中位 PFS 为 10.95 个月，而至少有一个变异等位基因 A 的患者为 5.44 个月（HR 3.30；95%CI：1.52-7.14；=0.001）。野生型 rs2236416 和 rs2274755 纯合子患者的中位 PFS 分别为 9.48 个月、6 个月和 6.62 个月，而至少有一个变异等位基因的患者分别为 6 个月和 6.62 个月（=0.022，=0.043）。携带野生型 rs2445365 的患者的 OS 也延长至 30.92 个月（=0.034），而携带至少一个变异等位基因 A 的患者的 OS 为 22.07 个月。这些基因变异能够预测接受贝伐单抗为基础的治疗的 mCRC 患者的临床结局和肿瘤反应。
