Abstract：
To identify candidate gene mutations to significantly predict the risk of survival prognosis after treatment with systemic first-line targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) patients.
Between 2005 and 2017, 168 triplet-tissue block samples from 56 mRCC patients were selected for targeted gene sequencing (TGS). Fifty-six patients\' medical records including overall survival (OS) and progression-free survival (PFS) at the time of mRCC diagnosis were evaluated. The patients were grouped into favorable (>12 months/>3 years), intermediate (3-12/12-36 months), and poor groups according to their PFS/OS (<3 months/<12 months). We identified any significant therapeutic targeted genes relating to the survival with a significance at p<0.050.
The first line therapeutic response showed 1.8% complete remission, 14.2% partial response, 42.9% stable disease, and 41.1% progressive disease. Among the overall TGS results, the cumulative effect of CDH1, and/or PTK2 genes significantly reflected the therapeutic responses in terms of PFS/OS; CDH1 and PTK2 mutations were associated with poor prognostic outcomes (p<0.050). Among only triplet-quality check passed tissues, the SGO2, BRAF, URB1, and NEDD1 mutated genes significantly correlated with OS. Regarding metastasis, patients with liver metastasis had the worst OS (p=0.050). The combinational mutation number from these two candidate genes in the liver metastatic samples with mutated EGFR2 and FABP7 also showed a significantly worse OS than those with other metastatic lesions (p<0.050).
This study reports several significant mutated genes related to the survival prognosis in mRCC patients treated with first-line TT.
Between 2005 and 2017, 168 triplet-tissue block samples from 56 mRCC patients were selected for targeted gene sequencing (TGS). Fifty-six patients\' medical records including overall survival (OS) and progression-free survival (PFS) at the time of mRCC diagnosis were evaluated. The patients were grouped into favorable (>12 months/>3 years), intermediate (3-12/12-36 months), and poor groups according to their PFS/OS (<3 months/<12 months). We identified any significant therapeutic targeted genes relating to the survival with a significance at p<0.050.
The first line therapeutic response showed 1.8% complete remission, 14.2% partial response, 42.9% stable disease, and 41.1% progressive disease. Among the overall TGS results, the cumulative effect of CDH1, and/or PTK2 genes significantly reflected the therapeutic responses in terms of PFS/OS; CDH1 and PTK2 mutations were associated with poor prognostic outcomes (p<0.050). Among only triplet-quality check passed tissues, the SGO2, BRAF, URB1, and NEDD1 mutated genes significantly correlated with OS. Regarding metastasis, patients with liver metastasis had the worst OS (p=0.050). The combinational mutation number from these two candidate genes in the liver metastatic samples with mutated EGFR2 and FABP7 also showed a significantly worse OS than those with other metastatic lesions (p<0.050).
This study reports several significant mutated genes related to the survival prognosis in mRCC patients treated with first-line TT.
摘要：
确定候选基因突变，以预测转移性肾细胞癌（mRCC）患者全身一线靶向治疗（TT）治疗后生存预后的风险。
在2005年至2017年之间，从56例mRCC患者中选择了168例三联体组织块样本进行靶向基因测序（TGS）。评估56例患者的医疗记录，包括mRCC诊断时的总生存期（OS）和无进展生存期（PFS）。患者被分组为有利的（>12个月/>3年），中级（3-12/12-36个月），根据他们的PFS/OS（<3个月/<12个月）和贫困人群。我们鉴定了与存活相关的任何显著的治疗靶向基因,在p<0.050处具有显著性。
一线治疗反应显示1.8%完全缓解，14.2%部分反应，42.9%病情稳定,和41.1%的进行性疾病。在总体TGS结果中，CDH1和/或PTK2基因的累积效应显著反映了PFS/OS方面的治疗反应;CDH1和PTK2突变与不良预后结局相关(p<0.050).在仅有的三重质量检查通过的组织中，SGO2，BRAF，URB1和NEDD1突变基因与OS显著相关。关于转移，肝转移患者的OS最差(p=0.050)。在具有突变的EGFR2和FABP7的肝转移样品中来自这两个候选基因的组合突变数目也显示出比具有其他转移性病变的那些显著更差的OS(p<0.050)。
本研究报道了一线TT治疗的mRCC患者中几个与生存预后相关的重要突变基因。
在2005年至2017年之间，从56例mRCC患者中选择了168例三联体组织块样本进行靶向基因测序（TGS）。评估56例患者的医疗记录，包括mRCC诊断时的总生存期（OS）和无进展生存期（PFS）。患者被分组为有利的（>12个月/>3年），中级（3-12/12-36个月），根据他们的PFS/OS（<3个月/<12个月）和贫困人群。我们鉴定了与存活相关的任何显著的治疗靶向基因,在p<0.050处具有显著性。
一线治疗反应显示1.8%完全缓解，14.2%部分反应，42.9%病情稳定,和41.1%的进行性疾病。在总体TGS结果中，CDH1和/或PTK2基因的累积效应显著反映了PFS/OS方面的治疗反应;CDH1和PTK2突变与不良预后结局相关(p<0.050).在仅有的三重质量检查通过的组织中，SGO2，BRAF，URB1和NEDD1突变基因与OS显著相关。关于转移，肝转移患者的OS最差(p=0.050)。在具有突变的EGFR2和FABP7的肝转移样品中来自这两个候选基因的组合突变数目也显示出比具有其他转移性病变的那些显著更差的OS(p<0.050)。
本研究报道了一线TT治疗的mRCC患者中几个与生存预后相关的重要突变基因。
