DPYD基因表达与胃癌患者5-氟尿嘧啶敏感性及毒副反应的相关性

Correlation of the gene expression of DPYD with 5-fluorouracil chemosensitivity and related toxic and side effects in gastric cancer patients

摘要:

目的 观察二氢嘧啶脱氢酶基因（DPYD）表达与胃癌患者5-氟尿嘧啶（5-FU）敏感性及毒副反应的相关性。方法 选取2018年1月—2023年1月在广安市人民医院治疗的胃癌患者60例，取新鲜切除的肿瘤非坏死组织。采用免疫组织化学法检测肿瘤组织DPYD表达强度，实时荧光定量聚合酶链反应检测DPYD mRNA表达，体外药敏试验检测胃癌原代细胞对5-FU的敏感性。术后均采用以5-FU为基础的综合化疗方案，化疗结束后统计化疗效果、毒副反应发生率及严重程度。比较不同DPYD表达强度患者5-FU敏感性；采用Pearson法分析DPYD mRNA表达与药敏指数的相关性；比较不同DPYD表达强度患者毒副反应。结果 60例患者的肿瘤组织中，DPYD低表达34例，高表达26例，高表达患者DPYD光密度值高于低表达患者（P <0.05）。DPYD低表达患者化疗总有效率、5-FU敏感率高于高表达患者（P <0.05）。DPYD mRNA表达与化疗效果（r =-0.664）、药敏指数（r_s=-0.892）呈负相关（P <0.05）。DPYD低表达患者3、4级上消化道反应、神经毒性、骨髓抑制、皮肤感染发生率高于高表达患者（P <0.05）。结论 DPYD基因高表达与胃癌患者5-FU敏感性降低有关，但毒副反应更轻。

Abstract:

Objective To observe the correlation of the gene expression of dihydropyrimidine dehydrogenase (DPYD) with 5-fluorouracil (5-FU) chemosensitivity and related toxic and side effects in gastric cancer patients.Methods Sixty gastric cancer patients treated in Guang'an People's Hospital from January 2018 to January 2023 were selected, and fresh non-necrotic tumor tissues were taken. Immunohistochemistry was used to detect the intensity of DPYD expression in tumor tissues, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of DPYD. In vitro drug sensitivity test was performed to measure the chemosensitivity of primary gastric cancer cells to 5-FU. After the surgery, all patients received a comprehensive chemotherapy based on 5-FU, and the efficacy of chemotherapy, and incidence and severity of toxic and side effects were analyzed following the chemotherapy. The chemosensitivity to 5-FU was compared among patients with different levels of DPYD expression. Pearson method was applied to analyze the correlation between the mRNA expression of DPYD and the sensitivity index. The toxic and side effects were also compared among patients with different levels of DPYD expression.Results Among the tumor tissues from 60 patients, 34 cases had a low expression of DPYD while 26 cases had a high expression of DPYD, and the optical density as shown by immunohistochemistry of patients with a high expression of DPYD was higher than that of patients with a low expression of DPYD (P < 0.05). The overall effective rate of the chemotherapy and the response rate of 5-FU in patients with a low expression of DPYD were higher than those in patients with a high expression of DPYD (P < 0.05). The mRNA expression of DPYD was negatively correlated with the efficacy of chemotherapy (r_s = -0.892) and the sensitivity index (r_s = -0.892) (P < 0.05). The incidence of grade 3 to 4 upper gastrointestinal adverse reactions, neurotoxicity, bone marrow suppression and skin infection in patients with a low expression of DPYD was higher than that in patients with a high expression of DPYD.Conclusions High gene expression of DPYD is correlated with reduced chemosensitivity of gastric cancer patients to 5-FU, but with milder toxic and side effects.