Pri-miR-378 rs1076064与肺癌铂类联合化疗毒副反应的相关性研究  

Pri-miR-378 rs1076064 Predicts Chemotherapy Toxicity Induced by Platinum in Lung Cancer Patients

作　　者：龚卫静 周涛 徐佳强 黄怡菲 吕永宁[1,2] 师少军 张玉[1,2] 伍三兰 GONG Wei-jing;ZHOU Tao;XU Jia-qiang;HUANG Yi-fei;LÜ Yong-ning;SHI Shao-jun;ZHANG Yu;WU San-lan(Department of Pharmacy,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;Hubei Province Clinical Research Center for Precision Medicine for Critical Illness,Wuhan 430022,China)

机构地区：[1]华中科技大学同济医学院附属协和医院药学部,武汉430022 [2]湖北省重大疾病精准用药医学研究中心,武汉430022

出　　处：《中国药学杂志》2022年第2期149-153,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(82003868);国家重点研发计划项目资助(2017YFC0909900);华中科技大学同济医学院附属协和医院研究基金项目资助(000005033)。

摘　　要：目的探讨pri-miR-378 rs1076064与肺癌铂类联合化疗毒副反应的相关性。方法本研究共纳入467名接受至少两个周期铂类化疗的肺癌患者,使用飞行时间质谱对rs1076064进行基因分型,使用无条件逻辑回归分析评估化疗后毒性反应与其基因型的相关性。结果研究发现,携带pri-miR-378 rs1076064 G等位基因的小细胞肺癌患者铂类联合化疗的总毒副反应风险增加(校正OR=2.744,95%CI=1.089~6.909,P=0.032);在分层分析中发现,pri-miR-378 rs1076064在依托泊苷联合铂类化疗(加性模型:校正OR=2.820,95%CI=1.119~7.103,P=0.028;显性模型:校正OR=6.105,95%CI=1.108~33.650,P=0.038)、以顺铂为基础的化疗(加性模型:校正OR=1.931,95%CI=1.026~3.636,P=0.041)、男性人群(显性模型:校正OR=2.120,95%CI=1.115~4.029,P=0.022)和小细胞肺癌(加性模型:校正OR=2.637,95%CI=1.066~6.524,P=0.036;显性模型:校正OR=8.912,95%CI=1.051~75.56,P=0.045)人群中与铂类联合化疗后血液毒副反应显著相关;但未见与胃肠道毒副反应的相关性。结论 pri-miR-378 rs1076064有可能作为预测中国肺癌相关患者人群铂类化疗血液毒性的候选生物标志物。OBJECTIVE To explore the association between pri-miR-378 rs1076064 and platinum-based chemotherapy toxicity in lung cancer patients. METHODS A total of 467 lung cancer patients with at least two cycles platinum-based chemotherapy were recruited. The Sequenom MassARRAY system was used to genotype pri-miR-378 rs1076064. Unconditional logistical regression analysis was conducted to assess the associations. RESULTS Small-cell lung cancer patients with pri-miR-378 rs1076064 G allele had an increased risk of total platinum-based chemotherapy toxicity(adjusted OR=2.744, 95%CI=1.089-6.909,P=0.032). Pri-miR-378 rs1076064 was associated with severe hematological toxicity in those with platinum + etoposide(additive model: adjusted OR=2.820, 95%CI=1.119-7.103,P=0.028;dominant model: adjusted OR=6.105, 95%CI=1.108-33.650,P=0.038), cisplatin(additive model: adjusted OR=1.931, 95%CI=1.026-3.636,P=0.041), male(dominant model: adjusted OR=2.120, 95%CI=1.115-4.029,P=0.022) and small-cell lung cancer(additive model: adjusted OR=2.637, 95%CI=1.066-6.524,P=0.036;dominant model: adjusted OR=8.912, 95%CI=1.051-75.56,P=0.045). The association between rs1076064 and severe gastrointestinal toxicity did not reach significance. CONCLUSIONS Pri-miR-378 rs1076064 may be considered as a potential biomarker for platinum-based chemotherapy hematology in some subpopulation lung cancer patients.

关 键 词：pri-miR-378 rs1076064 肺癌 铂类药物化疗 毒副反应 

分 类 号：R969.3[医药卫生—药理学]