分子标志对食管癌治疗的预测作用.doc

分子标志对食管癌治疗的预测作用Molecular Markers in Predicting the Treatment of Esophageal Cancer Department of Oncology, Henan Provincial Peoples Hospital, Zhengzhou, Henan Province, 450000 Cui Yao, Zhou Yun * * Corresponding author Abstract Recent years, the progressions to explore new effective markers and predictors in esophageal cancer at the molecular level unfold new scenery before clinical physicians. Sensitive and specific molecular markers to predict response to treatment in patients with esophageal cancer are found.Excision Repair Cross Complementing 1(ERCC 1), thymidylate synthase (TS) are used to predict effectiveness of cisplatin and fluorouracil in esophageal cancer patients. The expressions of P53 and NF-κB are related with the degrees of tumor malignancy and drug resistance. More other molecular markers, are described for selection and prognosis of chemotherapy / target therapy in individual patients, to determine the most effective and minimum adverse reaction chemotherapy regimens, and to obviate non- necessary or harmful agents for patients. Keyword esophageal cancer; molecular markers; chemotherapy; effects; prognosis 我国是食管癌的高发国家，随着卫生部门对食管癌预防医学的重视，食管癌早期诊断和治疗率较前明显上升，早期食管癌患者5年生存率可达90％以上，而中晚期仅10～15％。联合放化疗的治疗方式在食管癌的治疗方面获得了肯定。最常用的化疗为顺铂联合氟尿嘧啶的方案，放疗剂量45Gy-50Gy，大大延长了患者的生存期。在临床上我们常常可以见到肿瘤组织分化程度与预后不一致的病例，即组织分化较好的患者预后并不比分化差的患者好，而有些患者的临床TNM分期较优，却不能从放化疗中获得生存期的延长。提示形态病理学和临床TNM分期判断预后所存在的局限性。近年来，分子病理的发展为肿瘤预后的研究提供了新的手段。在分子水平上探索食管癌相关基因的变化，寻找敏感、特异的分子标志物，预测食管癌对治疗反应，对选择合适的患者群体，减少不必要的或者有害的治疗有着重大的意义。 一、切除修复交叉互补基因 1（ERCC 1） 切除修复交叉互补基因 1 ( excisi on repair cr oss2 comp lementati on group 1，ERCC1)是人类 DNA损伤修复基因，由于其编码蛋白质不具有核苷酸切除修复功能，所以常在研究中检测其 mRNA水平作为评价标准。ERCC1是检测顺铂耐药的重要基因。顺铂的作用机制是与 DNA分子形成PtDNA加成物干扰 DNA的复制与转录启动细胞程序性凋亡过程。ERCC1核苷酸切除修复顺铂耐药的重要机制。Kim 等报道ERCC1食管鳞癌的新辅助治疗是病理缓解的独立预测因子[1]，Warnecke-Eberz 等36 例食管癌患者的 ERCC1 表达情况发现 ERCC1 高表达患者对放化疗反应不敏感 ＜0．001 [ 2]。国内中山大学肿瘤防治中心的张兴等对根治性放化疗和术前放化疗食管癌病例的研究，仅发现中期有效率ERCC1的高表达趋势[3]。目前有研究表明 ERCC12 C8092AERCC12 C19007T位点的基因多态性和铂类药物的疗效相关。B ralbury等通过对 150