卵巢癌患者MMP-2基因rs243866,rs243842和rs243865位点多态性与含铂化疗方案疗效及不良反应的相关性研究

Association of rs243866,rs243842 and rs243865 Polymorphisms in MMP-2Gene with Response and Adverse Reactions of Platinum-based Chemotherapy in Advanced Ovarian Cancer

目的探讨卵巢癌(ovarian cancer)患者基质金属蛋白酶(matrix metalloproteinase,MMP)-2基因rs243866,rs243842和rs243865的多态性与其含铂化疗方案的疗效和不良反应的关系。方法选取2018年12月~2021年12月在海南医学院第二附属医院经病理确诊、一线接受含铂化疗方案治疗并具有完整资料的卵巢癌患者126例。化疗前采集患者3ml外周静脉血,采用多重PCR扩增目标区域后再进行高通量测序,鉴定rs243866,rs243842和rs243865的基因型。分析其与含铂方案疗效及不良反应的相关性。结果109例患者可评估疗效,其中完全缓解(complete response,CR)/部分缓解(partial response,PR)或疾病稳定(stable disease,SD)/疾病进展(progressive disease,PD)的患者分别为78例和31例。126例患者中发生Ⅲ~Ⅳ级血液学毒性和消化道毒性的分别有33例和16例。MMP-2基因rs243866多态性与含铂化疗方案的疗效及不良反应均相关,携带G等位基因的卵巢癌患者具有更好的疗效,其CR/PR率为74.6%,显著高于携带A等位基因(25.4%)的患者(OR=3.148,95%CI:1.362~7.441)。携带A等位基因的患者Ⅲ~Ⅳ级血液学毒性的发生率为60%,显著高于携带G等位基因(22.5%)的患者(OR=5.176,95%CI:2.193~12.217)。rs243842和rs243865位点各基因型分布及等位基因分布频次与含铂方案的疗效及不良反应均无相关性。结论携带rs243866 G等位基因的晚期卵巢癌患者在接受含铂方案治疗时具有较好的疗效和较低Ⅲ/Ⅳ血液学毒性。

Objective To evaluate the association of matrix metalloproteinase(MMP)-2 gene polymorphisms with response and adverse reactions of platinum-based chemotherapy in advanced ovarian cancer.Methods A total of 126 cases with pathologically confirmed at the Second Affiliated Hospital of Hainan Medical University during December 2018 to December 2021 were collected which received platinum-based chemotherapy and all of them with complete data.3ml of peripheral venous blood sample was obtained from each patient before chemotherapy,then single nucleotide polymorphism of rs243866,rs243842and rs243865 was conducted using high throughout sequencing technology.The relationship among the genotypes with chemotherapeutic response and adverse reactions was analyzed.Results 109 patients could be evaluated for curative effect,among which 78 patients were complete response(CR)/partial response(PR)and 31 patients were stable disease(SD)/progressive disease(PD).33 patients had gradeⅢ~Ⅳhematological toxicity and 16 patients had gradeⅢ~Ⅳgastrointestinal toxicity in all 126 patients.The polymorphism of rs243866 were related with the chemotherapeutic response and adverse reactions,and the chemotherapy CR/PR rate of patients with G allele was 74.6%.Compared with A allele(25.4%),individuals with G allele had a higher chemotherapy response(OR=3.148,95%CI:1.362~7.441).The incidence of gradeⅢ~Ⅳhematologic toxicity in patients with A allele was 60%,and carrying A allele(22.5%)was related with higher risk of hematologic toxicity(OR=5.176,95%CI:2.193~12.217).The polymorphisms of rs243842 and rs243865 were not statistically related with the chemotherapeutic response and adverse reactions.Conclusion Patients with advanced ovarian cancer who carried the rs243866 G allele had better efficacy andⅢ/Ⅳlower hematological toxicity when treated with platinum-based chemotherapy.