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

本研究采用定量双荧光免疫组织化学（qDFIHC）技术分析47例胃癌活检标本中5-氟尿嘧啶相关酶、TS、DPD和OPRT的表达，qDFIHC是一种新开发的定量蛋白表达系统。本研究首先确定了样本内的癌症异质性是否会影响qDFIHC系统的评估。随后，将TS、DPD、OPRT的表达值以及OPRT/TS、OPRT/DPD、OPRT/(TS+DPD)比值与患者的临床或病理反应进行回顾性分析。TS、DPD和OPRT在单场的表达值与三场的平均值显著相关。在分析的6个候选因素中，47例患者的临床反应与OPRT、OPRT/TS、OPRT/DPD和OPRT/(TS+DPD)有显著相关性。在四个因素中确定区分临床反应的临界值。OPRT/TS与临床反应相关性最强。qDFIHC能够量化肿瘤活检标本中TS、DPD和OPRT的表达，而不受异质性的影响。因此，在晚期胃癌患者中，根据OPRT/TS比例使用量身定制的S-1 NAC进行有效治疗有望实现。

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.