不同分子分型乳腺癌患者血清IGFBP-3、Angptl-2表达水平及其与骨转移、预后的相关性

The Expression Levels of Serum IGFBP-3 and Angptl-2 in Patients with Different Molecular Types of Breast Cancer and Their Correlation with Bone Metastasis and Prognosis

目的:分析不同分子分型乳腺癌患者血清胰岛素样生长因子结合蛋白3(IGFBP-3)、生成素养蛋白2(Angptl-2)表达水平及其与骨转移、预后的相关性。方法:选取2018年3月-2021年3月东南大学附属中大医院收治的128例乳腺癌骨转移患者进行研究,其中包括Luminal A型50例、42例Luminal B型(HER-2阴性)42例、HER-2过表达型16例、三阴性乳腺癌(TNBC)20例,并分析4种分子分型乳腺癌的临床病理特征,同时采用酶联免疫吸附法检测其血清IGFBP-3、Angptl-2表达水平;随访24个月后记录两组患者的预后情况,并采用多因素Logistic模型分析影响4种分子分型乳腺癌骨转移患者预后的独立危险因素,以及血清IGFBP-3、Angptl-2与不同分子分型乳腺癌骨转移患者预后的相关性。结果:Luminal A型、Luminal B型、HER-2过表达型、TNBC型TNM分期、淋巴结转移比较,差异有统计学意义(P<0.05)。与Luminal A型、Luminal B型、TNBC型乳腺癌骨转移患者相比,HER-2过表达型乳腺癌骨转移患者的血清IGFBP-3表达水平较低,Angptl-2表达水平较高(P<0.05)。Luminal A型、Luminal B型、HER-2过表达型、TNBC型乳腺癌骨转移患者的死亡率分别为13.46%、38.46%、23.08%、25.00%。多因素Logistic结果显示,TNM分期、淋巴结转移、血清IGFBP-3、Angptl-2均是影响不同分子分型乳腺癌骨转移患者预后的独立危险因素(P<0.05)。血清IGFBP-3异常高表达提示4种分子分型乳腺癌骨转移患者的不良预后,而Angptl-2表达水平与4种分子分型乳腺癌的预后呈正相关性(P<0.05)。针对不同分子分型乳腺癌骨转移患者的预后预测中,血清IGFBP-3、Angptl-2、IGFBP-3+Angptl-2均呈现AUC>0.75。结论:血清IGFBP-3、Angptl-2可作为HER-2过表达乳腺癌骨转移患者的潜在生物标志物;同时还可根据血清IGFBP-3、Angptl-2表达水平预测不同分子分型乳腺癌骨转移患者的预后。

Objective:To analyze the expression levels of serum insulin-like growth factor-binding protein 3(IGFBP-3)and angiopoietin 2(Angptl-2)and their correlation with bone metastasis and prognosis in patients with different molecularly typed breast cancer.Methods:One hundred and twenty-eight patients with breast cancer bone metastases admitted to Zhongda Hospital Southeast University(Jiangbei)from March 2018 to March 2021 were selected for the study,including 50 cases of Luminal A,42 cases of Luminal B(HER-2 negative),42 cases of HER-2 overexpression,16 cases of triple-negative breast cancer(TNBC),20 cases of TNBC,and analyzed the four molecular subtypes of breast cancer The clinicopathological characteristics of the four molecular subtypes of breast cancer were analyzed,and the expression levels of serum IGFBP-3 and Angptl-2 were detected by enzyme-linked immunosorbent assay;the prognosis of the two groups of patients was recorded after 24 months of follow-up,and a multifactorial logistic model was used to analyze the independent risk factors that affect the prognosis of patients with bone metastases of the four molecular subtypes of breast cancer and the correlation between serum IGFBP-3 and Angptl-2 and the prognosis of patients with bone metastases of different molecular subtypes of breast cancer.prognosis of patients with bone metastases from different molecular typing of breast cancer.Results:Luminal A type,Luminal B type,HER-2 overexpression type,and TNBC type TNM staging and lymph node metastasis were compared,and the difference was statistically significant(P<0.05).Compared with patients with breast cancer bone metastasis of Luminal A type,Luminal B type,and TNBC type,patients with breast cancer bone metastasis of HER-2 overexpression type had lower serum IGFBP-3 expression levels and higher Angptl-2 expression levels(P<0.05).Luminal A type,Luminal B type,HER-2 overexpression type,and TNBC type The mortality rates of patients with breast cancer bone metastases were 13.46%,38.46%,23.08%,and 25.00%,respectively.Multifactorial Logistic results showed that TNM stage,lymph node metastasis,serum IGFBP-3,and Angptl-2 were all independent risk factors affecting the prognosis of patients with bone metastasis from different molecular staging of breast cancer(P<0.05).Abnormally high expression of serum IGFBP-3 suggested poor prognosis in patients with bone metastases of the four molecular staging breast cancers,while the expression level of Angptl-2 was positively correlated with the prognosis of the four molecular staging breast cancers(P<0.05).For the prognostic prediction of patients with bone metastasis of different molecular typing breast cancer,serum IGFBP-3,Angptl-2,and IGFBP-3+Angptl-2 all showed AUC>0.75.Conclusion:Serum IGFBP-3 and Angptl-2 can be used as potential biomarkers for patients with HER-2 overexpression of breast cancer bone metastases;meanwhile,they can also be used to predict the prognosis of patients with breast cancer bone metastases of different molecular staging based on the expression levels of serum IGFBP-3 and Angptl-2.