卵巢透明细胞癌CA125应答、分子靶点与预后关联的多维度研究  

A multidimensional study on the relationships among CA125 response,molecular targets and prognosis in ovarian clear cell carcinoma

作　　者：丁红帆 徐桥 赵冰冰[1] 王毛毛 张洁清[1] DING Hongfan;XU Qiao;ZHAO Bingbing;WANG Maomao;ZHANG Jieqing(Department of Gynecology,Affiliated Cancer Hospital of Guangxi Medical University,Guangxi Key Laboratory of Early Prevention and Treatment of Regional High-incidence Tumors,Nanning,Guangxi 530021,China)

机构地区：[1]广西医科大学附属肿瘤医院妇科广西区域性高发肿瘤早期防治研究重点实验室,广西南宁530021

出　　处：《医药前沿》2025年第8期11-17,共7页Journal of Frontiers of Medicine

基　　金：广西医疗卫生适宜技术开发与推广应用项目(S2020094);广西自然科学基金项目(2023GXNSFAA026216)。

摘　　要：目的分析卵巢透明细胞癌(OCCC)糖类抗原125(CA125)应答、分子靶点与预后关联情况,为靶向治疗提供理论依据。方法回顾性分析2010年1月—2022年1月广西医科大学附属肿瘤医院诊治的63例OCCC患者的相关资料,包括年龄、绝经状态、是否合并子宫内膜异位症(EMs)、术前及术后CA125水平等。通过生物信息学方法分析酪氨酸激酶抑制剂(TKI)相互作用基因、与OCCC相关基因,构建蛋白相互作用网络,进行基因本体(GO)功能富集分析与京都基因和基因组数据库(KEGG)通路富集分析。采用免疫组化方法检测OCCC组织中分化簇117(CD117)、血管内皮生长因子受体2(VEGFR2)、成纤维细胞生长因子受体1(FGFR1)的表达水平。结果EMs的OCCC患者CA125水平低于不合并EMs的OCCC患者(P<0.05);CA125水平在第2个化疗周期内降至正常的患者与未降至正常的OCCC患者1、3、5年无进展生存期(PFS)和3、5年总生存期(OS)比较,差异有统计学意义(P<0.05);多因素分析结果显示,国际妇产科联盟(FIGO)分期、CA125水平在第2个化疗周期内降至正常及淋巴结转移是OCCC患者PFS和OS的影响因素(P<0.05)。生物信息学方法分析结果显示,OCCC与TKI靶点相关基因共408个。免疫组化结果显示,CD117、VEGFR2、FGFR1在OCCC组织中的阳性表达率分别为68.75%、63.63%、75.00%。结论CA125水平在第2个化疗周期内降至正常是评价PFS和OS的重要指标;FIGO分期、CA125水平在第2个周期化疗内降至正常及淋巴结转移是OCCC患者PFS和OS的影响因素;生物信息学方法有助于寻找OCCC的相互作用靶基因和靶向药物,为OCCC诊治提供理论基础;CD117、VEGFR2、FGFR1在OCCC组织中的阳性表达率高,有望成为靶向药物治疗的靶点。Objective To analyze the relationships among carbohydrate antigen 125(CA125)response,molecular targets and prognosis in ovarian clear cell carcinoma(OCCC)in order to provide theoretical basis for the targeted therapy.Methods The relevant data of 63 OCCC patients treated in Affiliated Cancer Hospital of Guangxi Medical University from January 2010 to January 2022 was retrospectively analyzed,which included age,menopausal status,whether or not combination of endometriosis(EMs),preoperative and postoperative CA125 levels,and so on.Bioinformatics was used to analyze the genes interacting with tyrosine kinase inhibitors(TKI)and OCCC-related genes,and a protein interaction network was constructed,and then gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed.Immunohistochemistry was used to detect the expressions of cluster of differentiation 117(CD117),vascular endothelial growth factor receptor 2(VEGFR2),and fibroblast growth factor receptor 1(FGFR1)in OCCC tissues.Results The CA125 levels in OCCC patients with combination of endometriosis(EMs)were lower than those in patients without combination of EMs(P<0.05).There were statistically significant differences in the values of 1-year,3-year,and 5-year progression-free survival(PFS)and 3-year and 5-year overall survival(OS)between patients whose CA125 levels returned to normal within the second cycle of chemotherapy and patients without nomal CA125 levels(P<0.05).The multivariate analysis showed that the International Federation of Gynecology and Obstetrics(FIGO)stage,the reduction of CA125 levels to normal within the second cycle of chemotherapy,and lymph node metastasis were influencing factors of the PFS and OS in OCCC patients(P<0.05).Bioinformatics analysis showed that there were 408 genes related to OCCC and TKI targets.Immunohistochemistry results showed that the positive expression rates of CD117,VEGFR2,and FGFR1 in OCCC tissues were 68.75%,63.63%,and 75.00%respectively.Conclu

关 键 词：卵巢透明细胞癌 酪氨酸激酶抑制剂 分化簇117 血管内皮生长因子受体2 成纤维细胞生长因子受体1 

分 类 号：R711[医药卫生—妇产科学]