乳腺癌改良根治术患者术后复发转移的危险因素及血清CA125、COX-2、sTNFR-P55的预测价值研究

摘要 目的：探讨乳腺癌改良根治术患者术后复发转移的危险因素及血清糖类抗原125（CA125）、环加氧酶-2（COX-2）、可溶性肿瘤坏死因子受体P55（sTNFR-P55）的预测价值。方法：对2014年1月至2016年12月新疆医科大学第一附属医院收治的109例行乳腺癌改良根治术的乳腺癌患者进行前瞻性研究，所有患者术后均随访5年，其中2例失访，107例完成随访。根据5年内患者复发转移情况将其分为复发转移组（n=31）和未复发转移组（n=76）。收集患者入院时的临床病理资料，采用电化学发光法检测术前血清CA125，采用酶联免疫吸附法检测术前血清COX-2、sTNFR-P55。采用logistic回归模型分析患者术后复发转移的影响因素，绘制受试者工作特征（ROC）曲线评估血清CA125、COX-2、sTNFR-P55对术后复发转移的预测价值。结果：复发转移组肿瘤直径＞5 cm、浸润性非特殊癌、脉管癌栓、雌激素受体（ER）/孕激素受体（PR）阴性、无内分泌治疗构成比、TNM分期IIIA期、腋窝淋巴结转移数量4~9个构成比高于未复发转移组（P<0.05）。复发转移组血清CA125、COX-2、sTNFR-P55水平高于未复发转移组（P<0.05）。多因素logistic回归分析结果显示，肿瘤直径＞5 cm、浸润性非特殊癌、TNM分期IIIA期、脉管癌栓、腋窝淋巴结转移数量4~9个、CA125升高、COX-2升高、sTNFR-P55升高是乳腺癌改良根治术患者术后5年内复发转移的独立危险因素（OR=1.318、1.213、1.223、1.137、1.257、1.241、1.313、1.351，P<0.05）。血清CA125、COX-2、sTNFR-P55均可有效预测乳腺癌术后复发转移，曲线下面积（AUC）分别为0.803、0.749、0.761，三指标联合预测术后复发转移的AUC为0.915，灵敏度和特异度分别为0.94、0.83。结论：肿瘤直径、浸润性非特殊癌、TNM分期、脉管癌栓、腋窝淋巴结转移数量以及术前血清CA125、COX-2、sTNFR-P55异常升高是乳腺癌改良根治术患者术后5年内复发转移的危险因素，术前血清CA125、COX-2、sTNFR-P55联合检测可预测乳腺癌改良根治术后的复发转移风险。

Risk Factors of Recurrence and Metastasis in Patients with Breast Cancer after Modified Radical Mastectomy and Predictive Value Study of Serum CA125, COX-2 and sTNFR-P55

ABSTRACT Objective: To study the risk factors of recurrence and metastasis in patients with breast cancer after modified radical mastectomy and the predictive value of serum carbohydrate antigen 125(CA125), cyclo-oxygenase-2 (COX-2), soluble tumor necrosis factor receptor-P55 (sTNFR-P55). Methods: 109 patients with breast cancer who underwent modified radical mastectomy in The First Affiliated Hospital of Xinjiang Medical University from January 2014 to December 2016 were prospectively studied. All patients were followed up for 5 years after operation, including 2 patients who were lost to follow-up, and 107 patients who completed follow-up. According to the recurrence and metastasis within 5 years, the patients were divided into recurrence and metastasis group (n=31) and non-recurrence and metastasis group (n=76). The clinicopathological data of the patients at admission were collected. Preoperative serum CA125 was detected by electrochemiluminescence method, and preoperative serum COX-2 and sTNFR-P55 were detected by enzyme-linked immunosorbent assay. Logistic regression model was used to analyze the influencing factors of postoperative recurrence and metastasis, and receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of serum CA125, COX-2 and sTNFR-P55 on postoperative recurrence and metastasis. Results: The tumor diameter greater than 5cm, invasive non-specific carcinoma, vascular tumor thrombus, estrogen receptor (ER)/progesterone receptor (PR) negative, the constituent ratio of no endocrine therapy, TNM stage IIIA, and the number of axillary lymph node metastases 4~9 in the recurrence and metastasis group were higher than those in the non-recurrence and metastasis group (P<0.05). The levels of serum CA125, COX-2 and sTNFR-P55 in the recurrence and metastasis group were higher than those in the non-recurrence and metastasis group (P<0.05). Multivariate logistic regression analysis showed that tumor diameter greater than 5cm, invasive non-specific carcinoma, TNM stage IIIA, vascular tumor thrombus, number of axillary lymph node metastases 4~9, increased CA125, increased COX-2, and increased sTNFR-P55 were independent risk factors for recurrence and metastasis within 5 years after modified radical mastectomy (OR=1.318, 1.213, 1.223, 1.137, 1.257, 1.241, 1.313, 1.351, P<0.05). Serum CA125, COX-2 and sTNFR-P55 could effectively predict postoperative recurrence and metastasis of breast cancer, and the area under the curve (AUC) was 0.803, 0.749 and 0.761, respectively. The AUC of combined prediction of postoperative recurrence and metastasis of the three indexes was 0.915, and the sensitivity and specificity were 0.94 and 0.83, respectively. Conclusion: Tumor diameter, invasive non-specific carcinoma, TNM stage, vascular tumor thrombus, number of axillary lymph node metastases, and abnormal elevation of preoperative serum CA125, COX-2, sTNFR-P55 are risk factors for recurrence and metastasis within 5 years after modified radical mastectomy. Combined detection of preoperative serum CA125, COX-2 and STNFR-P55 can predict the risk of recurrence and metastasis after modified radical mastectomy.