Hepcidin蛋白与乳腺癌骨转移的关系
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摘要
目的分析乳腺癌及乳腺癌骨转移患者的Hepcidin蛋白及相关指标,探讨Hepcidin在乳腺癌发生、发展中的作用。方法回顾性分析江苏省常州市第一人民医院乳腺癌骨转移患者25例、乳腺癌无骨转移患者30例及乳腺增生患者30例。比较3组患者Hb、Hepcidin、BMP-6、IL-6、s Tf R的差异。用ROC曲线分析评价Hepcidin、BMP-6、IL-6对乳腺癌骨转移的诊断价值。多因素Logistic回归分析比较各指标在乳腺癌骨转移的作用。结果 3组患者Hb、Hepcidin、BMP-6、IL-6、s Tf R差异有统计学意义(P <0.05)。对Hepcidin及BMP-6,乳腺癌骨转移组>乳腺癌无骨转移组>乳腺增生组;对IL-6,乳腺癌骨转移组>乳腺癌无骨转移组及乳腺增生组,但后两组比较差异无统计学意义(P>0.05);对Hb,乳腺癌骨转移组<乳腺癌无骨转移组<乳腺增生组;对于s Tf R,乳腺癌骨转移组<乳腺癌无骨转移组<乳腺增生组。ROC曲线分析发现Hepcidin对于乳腺癌骨转移均有较高诊断价值,且优于BMP-6、IL-6。多因素分析发现Hepcidin是乳腺癌骨转移的独立危险因素。结论Hepcidin与乳腺癌骨转移有较好的相关性,其诊断价值有待进一步研究。
Objective To investigate role of Hepcidin in bone metastases of breast cancer and its clinical significance. Methods A retrospective analysis of 25 breast cancer patients with bone metastases, 30 breast cancer patients without bone metastases, and 30 patients with breast hyperplasia was conducted. Levels of Hb, Hepcidin, BMP-6, IL-6, and sTfR were measured. Statistical analysis was performed to evaluate the diagnostic value of Hepcidin, BMP-6 and IL-6 in bone metastasis in breast cancer. Results Patients with bone metastasis experienced highest levels of Hepcidin, BMP-6 and IL-6, followed by patients without bone metastasis and patients with breast hyperplasia(P < 0.05). Patients with breast hyperplasia experienced highest levels of Hb and sTfR, followed by patients without bone metastasis and patients with breast hyperplasia(P < 0.05). ROC analysis showed that Hepcidin was superior to BMP-6 and IL-6 as a diagnostic marker for breast cancer with bone metastasis. Multivariate analysis showed that Hepcidin was an independent risk factor for breast cancer with bone metastasis. Conclusion Hepcidin may be a promising diagnostic biomarker for bone metastasis of breast cancer.
Objective To investigate role of Hepcidin in bone metastases of breast cancer and its clinical significance. Methods A retrospective analysis of 25 breast cancer patients with bone metastases, 30 breast cancer patients without bone metastases, and 30 patients with breast hyperplasia was conducted. Levels of Hb, Hepcidin, BMP-6, IL-6, and sTfR were measured. Statistical analysis was performed to evaluate the diagnostic value of Hepcidin, BMP-6 and IL-6 in bone metastasis in breast cancer. Results Patients with bone metastasis experienced highest levels of Hepcidin, BMP-6 and IL-6, followed by patients without bone metastasis and patients with breast hyperplasia(P < 0.05). Patients with breast hyperplasia experienced highest levels of Hb and sTfR, followed by patients without bone metastasis and patients with breast hyperplasia(P < 0.05). ROC analysis showed that Hepcidin was superior to BMP-6 and IL-6 as a diagnostic marker for breast cancer with bone metastasis. Multivariate analysis showed that Hepcidin was an independent risk factor for breast cancer with bone metastasis. Conclusion Hepcidin may be a promising diagnostic biomarker for bone metastasis of breast cancer.
引文
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[9]KAMAI T,TOMOSUGI N,ABE H,et al.Increased serum hepcidin-25 level and increased tumor expression of hepcidin mRNA are associated with metastasis of renal cell carcinoma[J].BMC Cancer,2009,(9):270.
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[11]ZHANG S,CHEN Y,GUO W,et al.Disordered hepcidinferroportin signaling promotes breast cancer growth[J].Cell Signal,2014,26(11):2539-2550.
[12]ALARMO E L,KALLIONIEMI A.Bone morphogenetic proteins in breast cancer:dual role in tumourigenesis[J].Endocr Relat Cancer,2010,17(2):R123-139.
[13]杨士军,谭维琴,鲍艳梅.CA153、IL-6及IL-8与乳腺癌骨转移相关性探讨[J].重庆医学,2011,40(4):355-356.
[14]FUTAKUCHI M,SINGH R K.Animal model for mammary tumor growth in the bone microenvironment[J].Breast Cancer,2013,20(3):195-203.
[15]AKHTARI M,MANSURI J,KA,GUISE T,et al.Biology of breast cancer bone metastasis[J].Cancer Biology&Therapy,2008,7(1):3-9.
[16]薛冬,何小舟,许贤林,等.Hepcidin蛋白与前列腺癌骨转移的相关性研究[J].中华泌尿外科杂志,2013,34(1):65-68.
[17]PIETRANGELO A.Hepcidin in human iron disorders:therapeutic implications[J].J Hepatol,2011,54(1):173-181.
[2]江泽飞,陈佳艺,牛晓辉,等.乳腺癌骨转移和骨相关疾病临床诊疗专家共识(2014版)[J].中国肺癌杂志,2014,95(4):241-247.
[3]ORLANDI R,de BORTOLI M,CINISELLI C M,et al.Hepcidin and ferritin blood level as noninvasive tools for predicting breast cancer[J].Ann Oncol,2014,25(2):352-357.
[4]CINISELLI C M,de BORTOLI M,TAVERNA E,et al.Plasma hepcidin in early-stage breast cancer patients:no relationship with interleukin-6,erythropoietin and erythroferrone[J].Expert Rev Proteomics,2015,12(6):695-701.
[5]TROUTT J S,RUDLING M,PERSSON L,et al.Circulating human hepcidin-25 concentrations display a diurnal rhythm,increase with prolonged fasting,and are reduced by growth hormone administration[J].Clin Chem,2012,58(8):1225-1232.
[6]GANZ T,OLBINA G,GIRELLI D,et al.Immunoassay for human hepcidin[J].Blood,2008,112(10):4292-4297.
[7]MAES K,NEMETH E,ROODMAN G D,et al.In anemia of multiple myeloma,hepcidin is induced by increased bone morphogenetic protein 2[J].Blood,2010,116(18):3635-3644.
[8]TANNO T,RABEL A,ALLEYNE M,et al.Hepcidin,anaemia,and prostate cancer[J].BJU Int,2011,107(4):678-679.
[9]KAMAI T,TOMOSUGI N,ABE H,et al.Increased serum hepcidin-25 level and increased tumor expression of hepcidin mRNA are associated with metastasis of renal cell carcinoma[J].BMC Cancer,2009,(9):270.
[10]PINNIX Z K,MILLER L D,WANG W,et al.Ferroportin and iron regulation in breast cancer progression and prognosis[J].Sci Transl Med,2010,2(43):43ra56.
[11]ZHANG S,CHEN Y,GUO W,et al.Disordered hepcidinferroportin signaling promotes breast cancer growth[J].Cell Signal,2014,26(11):2539-2550.
[12]ALARMO E L,KALLIONIEMI A.Bone morphogenetic proteins in breast cancer:dual role in tumourigenesis[J].Endocr Relat Cancer,2010,17(2):R123-139.
[13]杨士军,谭维琴,鲍艳梅.CA153、IL-6及IL-8与乳腺癌骨转移相关性探讨[J].重庆医学,2011,40(4):355-356.
[14]FUTAKUCHI M,SINGH R K.Animal model for mammary tumor growth in the bone microenvironment[J].Breast Cancer,2013,20(3):195-203.
[15]AKHTARI M,MANSURI J,KA,GUISE T,et al.Biology of breast cancer bone metastasis[J].Cancer Biology&Therapy,2008,7(1):3-9.
[16]薛冬,何小舟,许贤林,等.Hepcidin蛋白与前列腺癌骨转移的相关性研究[J].中华泌尿外科杂志,2013,34(1):65-68.
[17]PIETRANGELO A.Hepcidin in human iron disorders:therapeutic implications[J].J Hepatol,2011,54(1):173-181.