血清可溶性c-Met对三阴乳腺癌诊断和预后的评估价值

Value of serum soluble c-Met in the diagnosis and prognosis of triple negative breast cancer

目的通过检测三阴乳腺癌(TNBC)患者血清可溶性c-Met(s-Met)浓度,探讨s-Met对TNBC诊断和预后评估的临床价值。方法收集2018年1月—2022年3月本院肿瘤内科收治的117例TNBC患者的血清、组织样本和临床资料,另选择57例乳腺良性结节患者作为良性组,83名健康体检者作为对照组。收集良性组和对照组血清样本。采用免疫组织化学染色检测组织c-Met蛋白表达,酶联免疫吸附法检测血清s-Met浓度,利用受试者工作曲线(ROC)评价血清s-Met对三阴乳腺癌的诊断效能,Cox比例风险模型分析影响TNBC患者OS和DFS的独立危险因素。结果三阴乳腺癌组织c-Met蛋白阳性表达率(88.9%,104/117)明显高于癌旁组织(58.1%,68/117),差异有统计学意义(χ^(2)=28.438,P<0.001)。TNBC组血清s-Met浓度明显高于良性组和对照组,良性组血清s-Met浓度明显高于对照组,差异有统计学意义(P<0.05)。临界值为555.07 ng/ml时,血清s-Met鉴别三阴乳腺癌和乳腺良性结节的AUC为0.790,敏感性和特异性分别为62.39%和87.72%。临界值为457.89 ng/ml时,血清s-Met鉴别三阴乳腺癌和健康人群的AUC为0.903,敏感性和特异性分别为80.34%和87.95%。TNBC患者血清s-Met浓度与癌组织c-Met蛋白表达呈显著正相关(P<0.05)。血清s-Met浓度与TNBC患者肿瘤直径、淋巴结转移有关(P<0.05),与患者年龄、肿瘤类型、TNM分期、Ki-67指数、p53表达无关(P>0.05)。血清s-Met高浓度组总生存时间和无病生存时间较低浓度组明显缩短,差异有统计学意义(P<0.05)。Cox多因素分析显示,血清s-Met是影响阴乳腺癌OS和DFS的独立预后因素(P均<0.05)。结论TNBC患者血清s-Met浓度明显升高,高浓度s-Met与患者肿瘤直径、淋巴结转移有关;血清s-Met可作为TNBC早期诊断、临床预后评估的指标。

Objective To detect the levels of serum soluble c-Met(s-Met)in triple negative breast cancer(TNBC)patients,in order to assess its potential role for the prognosis and diagnosis of patients.Methods A total of 117 TNBC patients treated in the internal oncology department of the First People`s Hospital of Chuhzou from January 2018 to March 2022 were enrolled in the present study.The serum samples,tissues and clinical data from TNBC patients were collected.Meanwhile,the serum samples isolated from 57 patients with benign breast nodules were selected as the benign group,and 83 cases of health people were enrolled as the control group.The expression of c-Met protein in tissues was detected by Immunohistochemistry,the levels of serum s-Met were detected by ELISA assay.The diagnostic value of serum s-Met for distinguishing TNBC patients from those non-TNBC was performed by ROC.Cox proportional risk model was used to analyze independent risk factors for OS and DFS in TNBC patients.Results The positive rate of c-Met protein in tumour tissues(88.9%,104/117)was significantly higher than that in the adjacent tissues(58.1%,68/117)(χ^(2)=28.438,P<0.001).Serum s-Met concentrations in the TNBC group was significantly higher than that in the benign group and control group,and s-Met in the benign group significantly higher than that in the control group,the difference was statistically significant(P<0.05).Using 555.07ng/ml as a cut-off value,the AUC were 0.790,the sensitivity and specificity were 62.39%and 87.72%for s-Met to differentiate between TNBC patients and benign breast nodules patients.Using 457.89ng/ml as a cut-off value,the AUC were 0.903,the sensitivity and specificity were 80.34%and 87.95%for s-Met to differentiate between TNBC patients and healthy control.There was a positive correlation between c-Met expression and serum s-Met levels(P<0.05).Serum s-Met in TNBC patients was associated with tumor size and metastasis status(P<0.05),however,it was not correlate to serum s-Met and age,tumor type,TNM stage,Ki-67 index and p53 in TNBC patients(P>0.05).Up-regulated serum s-Met in patients with TNBC predicted worse overall survival(OS)and progression-free survival(PFS)(P<0.05).Multivariate Cox regression analysis showed that serum s-Met was the independent risk factor for the OS and DFS in patients with TNBC(all P<0.05).Conclusions Serum s-Met is significantly increased in TNBC patients,and high concentration of s-Met is associated with tumor diameter and lymph node metastasis in patients.Serum s-Met might be a potential biomarker for early diagnosis and prognosis assessmentof TNBC.