SFRP1基因多态性与卡瑞利珠单抗联合化疗治疗晚期非小细胞肺癌疗效、不良反应的相关性研究  

Correlation between SFRP1 gene polymorphism and efficacy and adverse reactions of carrelizumab combined with chemotherapy in advanced non-small cell lung cancer

作　　者：董敏 刘建萍[2] 尹冬虹[3] DONG Min;LIU Jianping;YIN Donghong(Department of Pharmacy,Central Hospital,China Railway 17th Bureau Group Co.,LTD.,Taiyuan 030032;Department of Pharmacy,the First Hospital of Shanxi Medical University,Taiyuan 030001,China;Department of Pharmacy,the Second Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]中铁十七局集团有限公司中心医院药剂科,太原030032 [2]山西医科大学第一医院药学部,太原030001 [3]山西医科大学第二医院药学部,太原030001

出　　处：《新疆医科大学学报》2023年第1期74-79,共6页Journal of Xinjiang Medical University

基　　金：山西省自然科学基金面上项目(201901D111393)。

摘　　要：目的探讨分泌型卷曲相关蛋白1(Secreted frizzled-related protein-1,SFRP1)基因多态性与卡瑞利珠单抗联合化疗治疗晚期非小细胞肺癌(NSCLC)疗效、不良反应的相关性。方法选取2019年3月—2021年12月于中铁十七局集团有限公司中心医院确诊并进行治疗的216例晚期NSCLC患者作为研究对象。收集患者一般人口学资料、临床资料和血液样本。对SFRP1基因的两个SNP位点rs7832767(C>T)、rs1127379(A>G)进行基因分型。采用定量实时荧光定量聚合酶链式反应检测法测定SFRP1基因mRNA的相对表达量。采用卡瑞利珠单抗联合化疗治疗3个周期后,评价疗效及不良反应。结果在216例接受卡瑞利珠单抗联合化疗治疗的患者中,客观有效率为14.81%(32/216),疾病控制率为84.72%(183/216),共92例(42.59%)患者发生不良反应。rs7832767位点的基因型分布在(CR+PR)和(SD+PD)组间比较差异无统计学意义(χ^(2)=5.766,P=0.056),相较于CC基因型患者,CT基因型、CT+TT基因型携带者的疗效较好(P<0.05);rs1127379位点的基因型分布在(CR+PR)和(SD+PD)组间比较差异有统计学意义(χ^(2)=8.773,P=0.012)。AG、GG、AG+GG基因型患者疗效显著优于AA基因型患者(P<0.05),GG基因型携带者的疗效也显著优于AA+AG基因型携带者(P<0.05)。rs7832767位点多态性与治疗后irAE发生情况无关(P均>0.05)。rs1127379位点的基因型分布在irAE未发生和发生组间比较差异有统计学意义(χ^(2)=18.740,P<0.001)。与AA基因型患者相比,AG、AG+GG基因型患者发生irAE的风险显著降低(P<0.05)。SFRP1基因rs7832767位点CC基因型患者的SFRP1基因mRNA表达水平显著低于CT和TT基因型(P<0.05),rs1127379位点AA、AG、GG基因型患者的mRNA相对表达量两两比较,结果显示任意两组间差异均有统计学意义(P<0.05)。SFRP1基因在(CR+PR)组中的相对表达量显著高于(SD+PD)组的相对表达量(P<0.05)。结论SFRP1基因多态性与晚期非小细胞肺癌患者卡瑞利珠�Objective To investigate the correlation between secreted Frizzled-related protein-1(SFRP1)gene polymorphism and the efficacy and adverse reactions of carrelizumab combined with chemotherapy in treatment of advanced non-small cell lung cancer(NSCLC).Methods A total of 216 patients with advanced NSCLC who were diagnosed and treated in the hospital from March 2019 to December 2021 were selected as research objects.General demographic data,clinical data and blood samples were collected.2 SNPS rs7832767(C>T)and RS1127379(A>G)of SFRP1 were genotyped.The relative expression level of SFRP1 gene mRNA was determined by quantitative real-time fluorescence quantitative polymerase chain reaction.After 3 cycles of carrilizumab combined with chemotherapy,the efficacy and adverse reactions were evaluated.Results In 216 patients receiving carrilizumab combined with chemotherapy,the objective effective rate was 14.81%(32/216),the disease control rate was 84.72%(183/216),a total of 92 patients(42.59%)had adverse reactions.There was no significant difference in genotype distribution of rs7832767 between(CR+PR)and(SD+PD)groups(χ^(2)=5.766,P=0.056).Compared with CC genotype,CT genotype and CT+TT genotype carriers had better efficacy(P<0.05).The genotype distribution of rs1127379 was significantly different between(CR+PR)and(SD+PD)groups(χ^(2)=8.773,P=0.012).The efficacy of AG,GG and AG+GG genotype was significantly better than that of AA genotype(P<0.05),and the efficacy of GG genotype carriers were also significantly better than that of AA+AG genotype carriers(P<0.05).rs7832767 polymorphism had no correlation with irAE occurrence after the treatment(all P>0.05).The genotype distribution of rs1127379 was significantly different between non-iraE and irAE groups(χ^(2)=18.740,P<0.001).Compared with AA genotype,the risk of irAE in AG and AG+GG genotype patients were significantly reduced(P<0.05).The mRNA expression level of SFRP1 gene in CC genotype patients with rs7832767 locus of SFRP1 gene were significantly lower than that of CT a

关 键 词：非小细胞肺癌 卡瑞利珠单抗 免疫治疗相关不良反应 疗效 

分 类 号：R734.2[医药卫生—肿瘤]