Prognostic significance of NQO 1 expression in esophageal squamous cell carcinoma after preoperative chemotherapy with cisplatin and 5-fluorouracil followed by curative esophagectomy
Prognostic significance of NQO 1 expression in esophageal squamous cell carcinoma after preoperative chemotherapy with cisplatin and 5-fluorouracil followed by curative esophagectomy
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发表时间：
2016
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通讯作者：
H. Ichikawa;S. Kosugi;Y. Hirose;Y. Matsuda;T. Ishikawa;T. Hanyu;K. Usui;Yusuke Muneoka;M. Nagahashi;J. Sakata;Takashi Kobayashi;H. Kameyama;T. Wakai
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作者：
H. Ichikawa;S. Kosugi;Y. Hirose;Y. Matsuda;T. Ishikawa;T. Hanyu;K. Usui;Yusuke Muneoka;M. Nagahashi;J. Sakata;Takashi Kobayashi;H. Kameyama;T. Wakai
NAD(P)H：醌氧化还原酶-1(NQO1)对抗癌药物，特别是恶性肿瘤中的顺铂或5-氟尿嘧啶等氧化应激诱导剂具有耐药性。在这里，我们评估了NQO1在食管鳞癌(ESCC)细胞中的表达与患者对顺铂和5-氟尿嘧啶(CF)术前化疗反应的关系，并阐明了NQO1表达在ESCC患者预后中的意义。我们回顾分析了40例食管癌根治性切除加淋巴结清扫术后行CF治疗的病例。用抗NQO1的单抗对手术切除标本进行免疫组织化学染色。在40例患者中有18例(45%)的肿瘤显示NQO1高表达(NQO1高表达组)。与NQO1低组(分别为72%和45%)相比，NQO1高组术前CF治疗的组织学反应较差，但差异无统计学意义(P=0.09)。高NQO1组食道切除术后3年无复发生存率显著低于低NQO1组(39%vs.76%；P<；0.01)。Cox比例风险模型显示NQO1高表达是独立的预后不良因素(HR=3.53；P=0.02)，pN3高表达是独立的预后不良因素(HR=14.7；P<；0.01)。NQO1表达的免疫组织化学评估有可能预测食管鳞癌患者在术前接受CF治疗后的治疗反应和预后。
NAD(P)H:quinone oxidoreductase-1 (NQO1) confers resistance to anticancer agents, particularly to oxidative stress inducers such as cisplatin or 5-fluorouracil in malignant tumors. Here we evaluated the association between NQO1 expression in esophageal squamous cell carcinoma (ESCC) cells and the patients’ responses to preoperative chemotherapy with cisplatin and 5-fluorouracil (CF), and we elucidated the prognostic significance of NQO1 expression in ESCC patients. We retrospectively analyzed the cases of 40 patients who underwent preoperative CF therapy followed by curative esophagectomy with lymphadenectomy. Immunohistochemistry of the surgically resected specimens was conducted using the primary monoclonal antibody against NQO1. Eighteen of the 40 patients (45%) had tumors that showed high NQO1 expression (NQO1-high group). The poorer histological response to preoperative CF therapy was dominant in the NQO1-high group compared to the NQO1-low group (72% and 45%, respectively) but the difference was not significant (P=0.09). The 3-year recurrence-free survival rate after esophagectomy in the NQO1-high group was significantly lower compared to the NQO1-low group (39% vs. 76%; P<0.01). A Cox proportional hazards model revealed that high NQO1 expression was an independent unfavorable prognostic factor (HR=3.53; P=0.02) as was pN3 (HR=14.7; P<0.01). The immunohistochemical evaluation of NQO1 expression has potential to predict the treatment response and prognosis in patients who undergo preoperative CF therapy followed by esophagectomy for ESCC.