Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: results of a multicenter study.
Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: results of a multicenter study.
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转移性结直肠癌一线化疗后ERCC1，DPYD和VEGFA mRNA的表达水平的变化：多中心研究的结果。
DOI：
10.18632/oncotarget.5227
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发表时间：
2015-10-20
期刊：
影响因子：
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通讯作者：
Kokudo N
中科院分区：
文献类型：
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作者：
Baba H;Baba Y;Uemoto S;Yoshida K;Saiura A;Watanabe M;Maehara Y;Oki E;Ikeda Y;Matsuda H;Yamamoto M;Shimada M;Taketomi A;Unno M;Sugihara K;Ogata Y;Eguchi S;Kitano S;Shirouzu K;Saiki Y;Takamori H;Mori M;Hirata T;Wakabayashi G;Kokudo N
我们之前的研究表明，奥沙利铂作为一线化疗可以增加肝结直肠癌（CRC）转移灶中的ERCC 1和DPD水平。其次，抗VEGF单克隆抗体贝伐单抗是否改变肿瘤VEGFA水平尚不清楚。我们进行了这项多中心观察性研究，以验证我们先前对ERCC 1和DPD的研究结果，并阐明VEGFA表达对bavacizumab给药的反应。在22家日本研究机构招募了346例肝转移CRC患者。175例既往接受过含奥沙利铂化疗的患者（化疗组）和171例既往未接受过化疗的患者（非化疗组）切除了肝转移瘤。采用实时定量RT-PCR检测ERCC 1、DPYD和VEGFA mRNA水平。化疗组ERCC 1 mRNA表达明显高于非化疗组（P = 0.033），且两者呈显著相关（斯皮尔曼相关系数= 0.42; P < 0.0001）。VEGFA表达水平在接受贝伐单抗治疗的患者中（n = 51）高于未接受贝伐单抗治疗的患者（n = 251）（P = 0.007）。这项研究证实，一线奥沙利铂为基础的化疗增加ERCC 1和DPYD的表达水平，潜在地提高后续治疗的化疗敏感性。我们还发现，贝伐单抗诱导VEGFA在肿瘤细胞中的表达，这表明将贝伐单抗治疗延长至首次进展后的生物学原理。
Our previous study showed that administering oxaliplatin as first-line chemotherapy increased ERCC1 and DPD levels in liver colorectal cancers (CRCs) metastases. Second, whether the anti-VEGF monoclonal antibody bevacizumab alters tumoral VEGFA levels is unknown. We conducted this multicenter observational study to validate our previous findings on ERCC1 and DPD, and clarify the response of VEGFA expression to bavacizumab administration. 346 CRC patients with liver metastases were enrolled at 22 Japanese institutes. Resected liver metastases were available for 175 patients previously treated with oxaliplatin-based chemotherapy (chemotherapy group) and 171 receiving no previous chemotherapy (non-chemotherapy group). ERCC1, DPYD, and VEGFA mRNA levels were measured by real-time RT-PCR. ERCC1 mRNA expression was significantly higher in the chemotherapy group than in the non-chemotherapy group (P = 0.033), and were significantly correlated (Spearman's correlation coefficient = 0.42; P < 0.0001). VEGFA expression level was higher in patients receiving bevacizumab (n = 51) than in those who did not (n = 251) (P = 0.007). This study confirmed that first-line oxaliplatin-based chemotherapy increases ERCC1 and DPYD expression levels, potentially enhancing chemosensitivity to subsequent therapy. We also found that bevacizumab induces VEGFA expression in tumor cells, suggesting a biologic rationale for extending bevacizumab treatment beyond first progression.