HOXB9在乳腺癌中的表达及其对预后的意义
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摘要
目的探讨HOXB9在乳腺癌组织中的表达情况,分析其与乳腺癌患者临床病理特征及预后的关系。方法采用免疫组织化学SP法检测133例,Western blot检测20例乳腺癌及相匹配癌旁组织中HOXB9的蛋白表达水平。分析其表达与临床病理特征和预后的关系。结果免疫组织化学结果和Western blot表明,HOXB9在乳腺癌组织中的表达明显高于其相匹配的癌旁组织。HOXB9高表达与ER、HER2、ki-67表达、淋巴结转移、复发率、Luminal-B型有关。单因素和多因素分析表明HOXB9表达与乳腺癌患者术后的总体生存率(OS)密切相关。结论 HOXB9在乳腺癌中的高表达与肿瘤进展及预后不良相关。它有望作为乳腺癌患者预后的预测指标。
Objective The purpose of this study was to investigate the expression of HOXB9 in breast cancer tissues and to analyze its relationship with clinicopathological features and prognosis of breast cancer patients.Methods Immunohistochemical SP method was used to detect the expression of HOXB9 protein in133 cases of breast cancer and corresponding adjacent tissues.The expression of HOXB9 protein in 20 cases of fresh breast cancer and corresponding adjacent tissues was detected by Western blot.The relationship between its expression and clinicopathological features and prognosis was analyzed.Results Immunohistochemical assay and Western blot suggested that the expression of HOXB9 in breast cancer tissues was significantly higher than the corresponding adjacent tissues.The high expression of HOXB9 in breast cancer tissues was significantly associated with ER,HER2,ki-67,lymph node status,recurrence rate and luminal B subtype.Univariate and multivariate analysis highlighted that the expression of HOXB9 was strongly correlated with the overall survival(OS)in patients undergoing breast cancer surgery.Conclusion The high expression of HOXB9 in breast cancer is associated with tumor poor progression and poor prognosis.It is expected to be a predictor of prognosis in breast cancer patients.
Objective The purpose of this study was to investigate the expression of HOXB9 in breast cancer tissues and to analyze its relationship with clinicopathological features and prognosis of breast cancer patients.Methods Immunohistochemical SP method was used to detect the expression of HOXB9 protein in133 cases of breast cancer and corresponding adjacent tissues.The expression of HOXB9 protein in 20 cases of fresh breast cancer and corresponding adjacent tissues was detected by Western blot.The relationship between its expression and clinicopathological features and prognosis was analyzed.Results Immunohistochemical assay and Western blot suggested that the expression of HOXB9 in breast cancer tissues was significantly higher than the corresponding adjacent tissues.The high expression of HOXB9 in breast cancer tissues was significantly associated with ER,HER2,ki-67,lymph node status,recurrence rate and luminal B subtype.Univariate and multivariate analysis highlighted that the expression of HOXB9 was strongly correlated with the overall survival(OS)in patients undergoing breast cancer surgery.Conclusion The high expression of HOXB9 in breast cancer is associated with tumor poor progression and poor prognosis.It is expected to be a predictor of prognosis in breast cancer patients.
引文
[1]KOHLER B A,SHERMAN R L,NADIA H,et al.Annual report to the nation on the status of cancer,featuring incidence of breast cancer subtypes by race/ethnicity,poverty,and state[J].J Natl Cancer Inst,2015,107(6):djv048.
[2]CHEN Y,LIU Y,WANG Y,et al.Quantification of STAT 3and VEGF expression for molecular diagnosis of lymph node metastasis in breast cancer.[J].Medicine,2017,96(45):e8488.
[3]PHILLIPP B,BERNHARD H.Epigenetic modification suppresses proliferation,migration and invasion of urothelial cancer cell lines[J].Oncology Letters,2016,12(3):1693-1700.
[4]PIAO J,CHEN L,QUAN T,et al.Superior efficacy of cotreatment with the dual PI3K/mTOR inhibitor BEZ235and histone deacetylase inhibitor trichostatin A against NSCLC:[J].Oncotarget,2016,7(37):60169-60180.
[5]QUINONEZ S C,INNIS J W.Human HOX gene disorders[J].Mol Genet Metab,2014,111(1):4-15.
[6]BHATLEKAR S,FIELDS J Z,BOMAN B M.HOX genes and their role in the development of human cancers[J].J Mol Med(Berl),2014,92(8):811-823.
[7]周薇,赵龙凤,徐恩伟.同源盒基因家族与肿瘤关系的研究进展[J].中国药物与临床,2016,16(4):532-535.
[8]SONG J,WANG T,XU W,et al.HOXB9acetylation at K27is responsible for its suppression of colon cancer progression[J].Cancer Lett,2018,426:63-72.
[9]ZHAN J,WANG P,NIU M,et al.High expression of transcriptional factor HoxB9predicts poor prognosis in patients with lung adenocarcinoma[J].Histopathology,2015,66(7):955-965.
[10]KELLY Z,MOLLER-LEVET C,MCGRATH S,et al.The prognostic significance of specific/r,HOX/r,gene expression patterns in ovarian cancer[J].Int J Cancer,2016,139(7):1608-1617.
[11]WANG S S,WUPUTRA K,LIU C J,et al.Oncogenic function of the homeobox A13-long noncoding RNA HOTTIP-insulin growth factor-binding protein 3axis in human gastric cancer[J].Oncotarget,2016,7(24):36049-36064.
[12]LEE J Y,HUR H,YUN H J,et al.HOXB5Promotes the Proliferation and Invasion of Breast Cancer Cells[J].Int J Biol Sci,2015,11(6):701-711.
[13]WANG J,SANG D,XU B,et al.Value of breast cancer molecular subtypes and Ki67expression for the prediction of efficacy and prognosis of neoadjuvant chemotherapy in a Chinese population[J].Medicine,2016,95(18):e3518.
[14]TAO M,CHEN S,ZHANG X,et al.Ki-67labeling index is a predictive marker for a pathological complete response to neoadjuvant chemotherapy in breast cancer:a Meta-analysis[J].Medicine,2017,96(51):e9384.
[15]ZHUSSUPOVA A,HAYASHIDA T,TAKAHASHI M,et al.An E2F1-HOXB9transcriptional circuit is associated with breast cancer progression[J].PLoS One,2014,9(8):e105285.
[16]CHANG Q,ZHANG L,HE C,et al.HOXB9induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif[J].Oncotarget,2015,6(40):42838-42853.
[17]VEGI N M,KLAPPACHER J,OSWALD F,et al.MEIS2is an Oncogenic partner in AML1-ETO-positive AML[J].Cell Reports,2016,16(2):498-507.
[18]GUO Y B,SHAO Y M,CHEN J,et al.Effect of overexpression of HOX genes on its invasive tendency in cerebral glioma[J].Oncology Lett,2016,11(1):75-80.
[2]CHEN Y,LIU Y,WANG Y,et al.Quantification of STAT 3and VEGF expression for molecular diagnosis of lymph node metastasis in breast cancer.[J].Medicine,2017,96(45):e8488.
[3]PHILLIPP B,BERNHARD H.Epigenetic modification suppresses proliferation,migration and invasion of urothelial cancer cell lines[J].Oncology Letters,2016,12(3):1693-1700.
[4]PIAO J,CHEN L,QUAN T,et al.Superior efficacy of cotreatment with the dual PI3K/mTOR inhibitor BEZ235and histone deacetylase inhibitor trichostatin A against NSCLC:[J].Oncotarget,2016,7(37):60169-60180.
[5]QUINONEZ S C,INNIS J W.Human HOX gene disorders[J].Mol Genet Metab,2014,111(1):4-15.
[6]BHATLEKAR S,FIELDS J Z,BOMAN B M.HOX genes and their role in the development of human cancers[J].J Mol Med(Berl),2014,92(8):811-823.
[7]周薇,赵龙凤,徐恩伟.同源盒基因家族与肿瘤关系的研究进展[J].中国药物与临床,2016,16(4):532-535.
[8]SONG J,WANG T,XU W,et al.HOXB9acetylation at K27is responsible for its suppression of colon cancer progression[J].Cancer Lett,2018,426:63-72.
[9]ZHAN J,WANG P,NIU M,et al.High expression of transcriptional factor HoxB9predicts poor prognosis in patients with lung adenocarcinoma[J].Histopathology,2015,66(7):955-965.
[10]KELLY Z,MOLLER-LEVET C,MCGRATH S,et al.The prognostic significance of specific/r,HOX/r,gene expression patterns in ovarian cancer[J].Int J Cancer,2016,139(7):1608-1617.
[11]WANG S S,WUPUTRA K,LIU C J,et al.Oncogenic function of the homeobox A13-long noncoding RNA HOTTIP-insulin growth factor-binding protein 3axis in human gastric cancer[J].Oncotarget,2016,7(24):36049-36064.
[12]LEE J Y,HUR H,YUN H J,et al.HOXB5Promotes the Proliferation and Invasion of Breast Cancer Cells[J].Int J Biol Sci,2015,11(6):701-711.
[13]WANG J,SANG D,XU B,et al.Value of breast cancer molecular subtypes and Ki67expression for the prediction of efficacy and prognosis of neoadjuvant chemotherapy in a Chinese population[J].Medicine,2016,95(18):e3518.
[14]TAO M,CHEN S,ZHANG X,et al.Ki-67labeling index is a predictive marker for a pathological complete response to neoadjuvant chemotherapy in breast cancer:a Meta-analysis[J].Medicine,2017,96(51):e9384.
[15]ZHUSSUPOVA A,HAYASHIDA T,TAKAHASHI M,et al.An E2F1-HOXB9transcriptional circuit is associated with breast cancer progression[J].PLoS One,2014,9(8):e105285.
[16]CHANG Q,ZHANG L,HE C,et al.HOXB9induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif[J].Oncotarget,2015,6(40):42838-42853.
[17]VEGI N M,KLAPPACHER J,OSWALD F,et al.MEIS2is an Oncogenic partner in AML1-ETO-positive AML[J].Cell Reports,2016,16(2):498-507.
[18]GUO Y B,SHAO Y M,CHEN J,et al.Effect of overexpression of HOX genes on its invasive tendency in cerebral glioma[J].Oncology Lett,2016,11(1):75-80.