血清CA125和HE4的动态变化在预测卵巢高级别浆液性腺癌无进展生存期方面的价值研究  

A study on the value of dynamic changes of serum CA125 and HE4 in predicting the progression-free survival time of high-grade serous ovarian carcinoma

作　　者：何乐伟 王充 杨诗敏 张春晓 席晓薇 HE Lewei;WANG Chong;YANG Shimin;ZHANG Chunxiao;XI Xiaowei(Department of Obstetrics and Gynecology,Shanghai General Hospital of Nanjing Medical University,Shanghai 200080;Department of Obstetrics and Gynecology,the First People’s Hospital Affiliated with Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China)

机构地区：[1]南京医科大学附属上海一院临床医学院妇产科,上海200080 [2]上海交通大学医学院附属第一人民医院妇产科,上海200080

出　　处：《南京医科大学学报（自然科学版）》2024年第9期1207-1216,共10页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81772767)。

摘　　要：目的:研究血清糖类抗原125(carbohydrate antigen 125,CA125)和人附睾蛋白4(human epididymal protein 4,HE4)在术前以及术后化疗过程中的动态变化与卵巢癌患者无进展生存期(progression-free survival,PFS)及铂敏感性之间的关系。方法:回顾性分析上海交通大学医学院附属第一人民医院妇科肿瘤病房收治的经过规范化治疗的卵巢癌患者术前、术后化疗前,以及化疗中至少2次血清CA125及HE4水平,并收集对铂类药物敏感性、PFS等数据。主要统计学方法包括卡方检验、t检验、方差分析和Logistic回归分析及Cox比例风险回归分析等。结果:对117例卵巢高级别浆液性腺癌患者的分析结果提示,CA125和HE4阳性与肿瘤较高期别、多腹水量、不满意减灭、腹水细胞学阳性相关。通过Cox回归分析验证得出CA125和HE4均是预后的危险因素(OR=4.29,P=0.010;OR=1.77,P=0.049)。CA125、HE4均阳性患者组与仅CA125阳性的患者组比较,预后差异无统计学意义(P>0.05)。根据公式t_(1/2)=t_(1)/[2×lg(c_(1)/c_(2))]计算CA125和HE4半衰期,截取术前CA125和HE4、术后CA125和HE4最低值、CA125和HE4半衰期的最优cut-off值,分别为436 U/L和400 pmol/L、12 U/L和35 pmol/L、21 d和25 d,预后分析提示除了HE4最低值与预后无关,其余均和预后相关,其中CA125半衰期>21 d的HR值最高为3.28,中位PFS下降57.5%(P<0.001)。通过绘制受试者工作特征曲线计算曲线下面积(area under the curve,AUC),CA125半衰期>21 d(AUC=0.76)、CA125最低值>12 U/L(AUC=0.70)及第3程化疗后CA125未回归正常(AUC=0.71)这3项指标对于预测存在3年内复发有一定的临床价值,其灵敏度分别为71.8%、68.3%、68.2%,特异度分别为79.6%、71.7%、72.6%。结论:CA125半衰期、CA125化疗过程中最低值、第3程化疗后CA125未回归正常及6项指标中≥2项阳性这4个指标对于预测存在3年内复发有一定的临床价值,而对于预测铂敏感性的价值有待进一步探索。Objective:To investigate the dynamic changes of serum carbohydrate antigen 125(CA125)and human epididymal protein 4(HE4)levels before and after surgery and during chemotherapy,and their relationship with progression-free survival(PFS)and platinum sensitivity in patients with ovarian cancer.Methods:A retrospective analysis was conducted on serum CA125 and HE4levels before surgery,before chemotherapy,and at least twice during chemotherapy in standardized treated patients with ovarian cancer in the gynecologic oncology department of the First People's Hospital Affiliated with Shanghai Jiao Tong University School of Medicine.Data on platinum drug sensitivity and PFS were collected.The main statistical methods included chi-square test,t-test,logistic regression analysis,and Cox proportional hazards regression analysis.Results:The analysis of 117 patients with high-grade serous ovarian cancer suggested that CA125 and HE4 positivity were associated with higher stage,greater ascites volume,unsatisfactory surgical debulking,and positive ascites cytology.Cox regression analysis verified that both CA125 and HE4 are prognostic risk factors(OR=4.29,P=0.010;OR=1.77,P=0.049).Patients with both CA125 and HE4 positive and those with only CA125 positive showed no significant difference in prognosis(P > 0.05).The half-life of CA125 and HE4 were calculated using the formula t1/2=t1/[2×lg(c1/c2)].The optimal cut-offs for preoperative and postoperative CA125 and HE4,and the half-life of CA125 and HE4 were determined by X-tile and were 436 U/L,400 pmol/L,12 U/L,35 pmol/L,21 days,and 25 days,respectively.The prognostic analysis showed that except for the lowest value of HE4,all other factors were related to prognosis.The highest HR value was 3.28 for CA125 half-life >21 days,with a decrease of 57.5% in median PFS(P < 0.001).The area under the curve(AUC)was calculated by plotting the receiver operating characteristic(ROC)curve.ROC curve analysis showed that CA125 half-life >21 days(AUC=0.76),CA125 lowest value >12 U/L(AUC=0.70),and fail

关 键 词：卵巢高级别浆液性腺癌 无进展生存期 CA125 HE4 临床研究 

分 类 号：R737.31[医药卫生—肿瘤]