二氢嘧啶脱氢酶在胃癌组织中的表达及临床意义
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摘要
目的探讨二氢嘧啶脱氢酶(DPD)在胃癌组织中的表达及临床意义。方法采用免疫组化法分别检测140例胃癌组织和90例癌旁组织中DPD表达情况,并分析胃癌组织中DPD表达与临床病理特征、疗效、不良反应和预后的关系。结果 DPD在胃癌组织中阳性表达率为84. 29%(118/140),癌旁胃黏膜正常组织中阳性表达率为46. 67%(42/90),差异具有统计学意义(P<0. 05)。胃癌组织中DPD阳性表达与患者年龄、性别、肿瘤大小、分化程度、浸润深度、淋巴结转移、分期等临床病理特征无关(P>0. 05)。可评价的84例DPD表达阳性胃癌患者化疗有效率为20. 24%(17/84),明显低于DPD阴性表达患者的59. 09%(13/22,P<0. 05)。DPD阳性表达患者的恶心、呕吐、口腔黏膜炎、腹泻等化疗不良反应发生率明显低于DPD阴性患者,差异具有统计学意义(P<0. 05)。DPD阳性与阴性表达组1年生存率分别为23. 73%(28/118)与68. 18%(15/22),差异具有统计学意义(P<0. 05)。结论胃癌组织中DPD阳性表达率明显高于癌旁组织,DPD在胃癌组织中的阳性表达率与临床病理特征无关,但DPD高表达患者5-氟尿嘧啶(Fu)化疗后不良反应更小,但其疗效和预后更差。DPD可作为5-Fu化疗敏感性、毒副反应和预后的一个指标,为个体化治疗方案的制定提供理论依据。
引文
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2包泱,常家聪,王道斌.MIF、MMP-9在胃癌组织中的表达及临床意义[J].安徽医科大学学报,2014;49(3):363-6.
3姚勤,邓杨林,吴迪,等.HPLC法间接测定肿瘤患者外周血中二氢嘧啶脱氢酶的活性[J].中国药房,2012;23(22):2045-6.
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6邓建忠,华东,黄朝晖,等.二氢嘧啶脱氢酶在胃癌组织中的表达及其临床意义[J].苏州大学学报(医学版),2008;28(1):65-7.
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9 Morita T,Matsuzaki A,Tokue A.Quantitative analysis of thymidine phosphorylase and dihydropyrimidine dehydrogenase in renal cell carcinoma[J].Oncology,2003;65(2):125-31.
10刘新兰,丛芳圆,王宁菊,等.胃癌组织中TS、DPD的表达及其临床意义[J].陕西医学杂志,2011;40(3):270-3.
11艾晓晴,贾喜花,王晓博,等.DPD和p53蛋白在结肠癌中的表达及预后分析[J].中国热带医学,2015;15(11):1379-82.
12 Zhao H,Zhao Y,Guo Y,et al.Clinical significance of the thymidylate synthase,dihydropyrimidine dehydrogenase,and thymidine phosphorylase mRNA expressions in hepatocellular carcinoma patients receiving 5-fluorouracil-based transarterial chemoembolization treatment[J].Oncol Targets Ther,2013;6(6):811-8.
13 Tanaka K,Saigusa S,Toiyama Y,et al.TS and DPD mRNA levels on formalin-fixed paraffin-embedded specimens as predictors for distant recurrence of rectal cancer treated with preoperative chemoradiotherapy[J].J Surg Oncol,2012;105(6):529-34.
14 Mekata E,Murata S,Sonoda H,et al.Protein-bound polysaccharideK augments the anticancer effect of fluoropyrimidine derivatives possibly by lowering dihydropyrimidine dehydrogenase expression in gastrointestinal cancers[J].Oncol Rep,2013;30(6):2845-51.
15陈英华,傅建伟,邓媛,等.晚期胃癌患者外周血中TS和DPDmRNA的表达对替吉奥化疗效果的影响[J].重庆医学,2013;42(12):1357-9.
16 Bocci G,Barbara C,Vannozzi F,et al.A pharmacokinetic-based test to prevent severe 5-fluorouracil toxicity[J].Clin Pharmacol Ther,2006;80(4):384-95.
17 Goto T,Shimmura K,Yokomizo K,et al.Thymidine phosphorylase in patients with colorectal cancer[J].Anticancer Res,2012;32(5):1757-62.
18练炼,慎晓明,周冲,等.胃癌患者血清DPD mRNA和TS mRNA蛋白对替吉奥疗效预测价值分析[J].中华肿瘤防治杂志,2015;22(5):368-72.
2包泱,常家聪,王道斌.MIF、MMP-9在胃癌组织中的表达及临床意义[J].安徽医科大学学报,2014;49(3):363-6.
3姚勤,邓杨林,吴迪,等.HPLC法间接测定肿瘤患者外周血中二氢嘧啶脱氢酶的活性[J].中国药房,2012;23(22):2045-6.
4鲁明骞,徐光川.二氢嘧啶脱氢酶在胃癌中的研究现状[J].世界华人消化杂志,2006;14(34):3290-3.
5 Oeda M,Yoshida K,Sanada Y,et al.The expression profiles of orotate phosphoribosyltransferase and dihydropyrimidine dehydrogenase in gastric cancer and their clinical significance[J].Oncol Rep,2006;16(6):1165-72.
6邓建忠,华东,黄朝晖,等.二氢嘧啶脱氢酶在胃癌组织中的表达及其临床意义[J].苏州大学学报(医学版),2008;28(1):65-7.
7 Fromowitz FB,Uiola MV,Choao S,et al.Ras p21expression in the progression of breast Cancer[J].Hum Pathol,1987;18(12):1268-75.
8鲁明骞,王杰,向丽娥,等.内源性二氢尿嘧啶与尿嘧啶比值在5-Fu化疗中毒性关系的临床研究[J].肿瘤防治研究,2007;34(4):197.
9 Morita T,Matsuzaki A,Tokue A.Quantitative analysis of thymidine phosphorylase and dihydropyrimidine dehydrogenase in renal cell carcinoma[J].Oncology,2003;65(2):125-31.
10刘新兰,丛芳圆,王宁菊,等.胃癌组织中TS、DPD的表达及其临床意义[J].陕西医学杂志,2011;40(3):270-3.
11艾晓晴,贾喜花,王晓博,等.DPD和p53蛋白在结肠癌中的表达及预后分析[J].中国热带医学,2015;15(11):1379-82.
12 Zhao H,Zhao Y,Guo Y,et al.Clinical significance of the thymidylate synthase,dihydropyrimidine dehydrogenase,and thymidine phosphorylase mRNA expressions in hepatocellular carcinoma patients receiving 5-fluorouracil-based transarterial chemoembolization treatment[J].Oncol Targets Ther,2013;6(6):811-8.
13 Tanaka K,Saigusa S,Toiyama Y,et al.TS and DPD mRNA levels on formalin-fixed paraffin-embedded specimens as predictors for distant recurrence of rectal cancer treated with preoperative chemoradiotherapy[J].J Surg Oncol,2012;105(6):529-34.
14 Mekata E,Murata S,Sonoda H,et al.Protein-bound polysaccharideK augments the anticancer effect of fluoropyrimidine derivatives possibly by lowering dihydropyrimidine dehydrogenase expression in gastrointestinal cancers[J].Oncol Rep,2013;30(6):2845-51.
15陈英华,傅建伟,邓媛,等.晚期胃癌患者外周血中TS和DPDmRNA的表达对替吉奥化疗效果的影响[J].重庆医学,2013;42(12):1357-9.
16 Bocci G,Barbara C,Vannozzi F,et al.A pharmacokinetic-based test to prevent severe 5-fluorouracil toxicity[J].Clin Pharmacol Ther,2006;80(4):384-95.
17 Goto T,Shimmura K,Yokomizo K,et al.Thymidine phosphorylase in patients with colorectal cancer[J].Anticancer Res,2012;32(5):1757-62.
18练炼,慎晓明,周冲,等.胃癌患者血清DPD mRNA和TS mRNA蛋白对替吉奥疗效预测价值分析[J].中华肿瘤防治杂志,2015;22(5):368-72.