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A quantitative evaluation of the determinant proteins for drug responsiveness assists in patient selection to chemotherapy in advanced gastrointestinal cancer

药物反应性决定蛋白的定量评估有助于晚期胃肠癌患者选择化疗

基本信息

批准号：
20591631
负责人：
KOHJI Miyazaki
金额：
$ 3.08万
依托单位：
Saga University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

项目摘要

The present study analyzed the expression of 5-fluorouracil related enzymes, TS, DPD and OPRT in 47 gastric cancer biopsy specimens using quantitative double-fluorescence immunohistochemistry (qDFIHC), which is a newly developed system to quantify protein expression. The study first determined whether the cancer heterogeneity within the sample influences evaluationby qDFIHC system. Thereafter, the expression values of the TS, DPD, OPRT and OPRT/TS, OPRT/DPD, OPRT/(TS+DPD) ratios were retrospectively correlated with the clinical or pathological response in the patients. The expression values of TS, DPD and OPRT at a single field were significantly correlated with mean of the values evaluated at three fields. Among the 6 candidate factors analyzed, OPRT, OPRT/TS, OPRT/DPD and OPRT/(TS+DPD) showed significant correlations with the clinical response in 47 patients. Cut-off values to differentiate the clinical response were determined in the four factors. OPRT/TS showed the strongest correlation with the clinical response. qDFIHC was able to quantify the TS, DPD and OPRT expressions in cancer biopsy specimens without being affected by the heterogeneity. Effective therapy using tailored S-1 NAC accordingto the OPRT/TS ratio is therefore expected in advanced gastric cancer patients.

本研究采用定量双荧光免疫组化（qDFIHC）技术对47例胃癌活检标本中5-氟尿嘧啶相关酶、TS、DPD和OPRT的表达进行了分析。本研究首先确定样本内的癌症异质性是否影响qDFIHC系统的评估。随后，将TS、DPD、OPRT和OPRT/TS、OPRT/DPD、OPRT/（TS+DPD）比值的表达值与患者的临床或病理反应进行回顾性相关。TS、DPD和OPRT在单个视野的表达值与在三个视野评估的值的平均值显著相关。在分析的6个候选因素中，OPRT、OPRT/TS、OPRT/DPD和OPRT/（TS+DPD）与47例患者的临床应答显著相关。在四个因素中确定区分临床应答的临界值。OPRT/TS显示与临床反应的最强相关性。qDFIHC能够定量癌症活检标本中的TS、DPD和OPRT表达，而不受异质性的影响。因此，根据OPRT/TS比值使用定制的S-1 NAC对进展期胃癌患者进行有效治疗是有希望的。