上皮性卵巢癌组织中KDF1表达及临床意义  

Expression and clinical significance of KDF1 in epithelial ovarian cancer

作　　者：曾尚云 卢烨[1] 安晓燕[2] ZENG Shangyun;LU Ye;AN Xiaoyan(Department of Gynecology,Datong Fifth People s Hospital,Datong 037009,China)

机构地区：[1]大同市第五人民医院妇科,山西大同037009 [2]大同市第五人民医院病理科,037009

出　　处：《临床肿瘤学杂志》2023年第6期495-501,共7页Chinese Clinical Oncology

摘　　要：目的 探讨角化细胞分化因子1(KDF1)在上皮性卵巢癌(EOC)组织中表达与辅助化疗耐药和预后的关系。方法 收集癌症基因组图谱(TCGA)数据库中的数据(n=379)分析EOC中KDF1 mRNA的表达模式和预后价值。收集大同市第五人民医院病理科135例福尔马林固定石蜡包埋组织,包括111例EOC组织,12例卵巢良性肿瘤组织和12例卵巢畸胎瘤组织。采用免疫组化染色法检测组织KDF1表达。患者化疗结束后,采用实体肿瘤疗效评价标准1.1版评估辅助化疗反应,完全缓解(CR)和部分缓解(PR)纳入敏感亚组,疾病稳定(SD)和疾病进展(PD)纳入耐药亚组。结果 通过对TCGA数据库中的卵巢癌数据进行差异表达分析,发现KDF1在卵巢癌患者中呈高表达(P<0.001),并与卵巢癌患者较低的总体生存率(OS)相关。在临床验证队列中,EOC组织中KDF1蛋白表达明显高于畸胎瘤组织和卵巢良性肿瘤组织(P<0.001)。根据KDF1免疫染色强度评分中位值,将EOC患者分为KDF1低表达组(<7.67分)和高表达组(≥7.67分)。辅助化疗耐药亚组组织KDF1蛋白评分显著高于敏感亚组(P<0.001)。当KDF1蛋白评分≥7.77分时可良好地预测辅助化疗耐药的风险,ROC曲线下面积为0.875(95%CI:0.812~0.937),灵敏度和特异度分别为86.80%和72.60%。Cox风险比例回归模型分析结果显示,KDF1高表达是预测EOC患者OS和PFS的独立影响因素(P<0.05)。KDF1低表达组和高表达组患者中位OS分别为37.98、16.18个月;中位PFS分别为18.95、11.51个月,差异均有统计学意义(P<0.05)。结论 组织中KDF1高表达与EOC患者辅助化疗耐药和不良预后风险更高有关,可能是潜在的预测生物标志物。Objective To investigate the relationship between expression of keratinocyte differentiation factor 1(KDF1)and adjuvant chemotherapy resistance and prognosis in epithelial ovarian cancer(EOC).Methods The expression pattern and prognostic value of KDF1 mRNA in Cancer Genome Atlas(TCGA)were analyzed using data(n=379).One hundred and thirty-five formalin paraffin-embedded tissues were collected from the pathology department of Datong Fifth People s Hospital,including 111 cases of EOC,12 cases of ovarian benign tumor and 12 cases of ovarian teratoma.The expression of KDF1 in tissues was detected by immunohistochemical staining.After the end of chemotherapy,solid tumor efficacy evaluation criteria version 1.1 was used to evaluate the response to adjuvant chemotherapy.Complete response(CR)and partial response(PR)were included in the sensitive subgroup,and stable disease(SD)and disease progression(PD)were included in the drug-resistant subgroup.Results By differential expression analysis of ovarian cancer data in the TCGA database,it was found that KDF1 was highly expressed in ovarian cancer patients(P<0.001)and was associated with lower overall survival rate(OS).In the clinical validation cohort,the expression of KDF1 protein in EOC tissues was significantly higher than that in teratoma tissues and ovarian benign tumors(P<0.001).According to the median value of KDF1 immunostaining intensity score,patients with EOC were divided into low expression group(<7.67 points)and high expression group(≥7.67 points).The KDF1 protein score in adjuvant chemotherapy resistant subgroup was significantly higher than that in sensitive subgroup(P<0.001).When KDF1 protein score≥7.77,the risk of adjuvant chemotherapy resistance could be well predicted.The area under ROC curve was 0.875(95%CI:0.812-0.937),and the sensitivity and specificity were 86.80%and 72.60%,respectively.Cox proportional regression analysis showed that high expression of KDF1 was an independent factor for predicting OS and PFS in patients with EOC(P<0.05).The median

关 键 词：上皮性卵巢癌 角化细胞分化因子1 辅助化疗 预后 

分 类 号：R737.31[医药卫生—肿瘤]