gata3基因表达与人乳腺肿瘤病理特征的相关性分析
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摘要
为了检测gata3基因在不同乳腺肿瘤组织中的相对表达情况,分析gata3基因表达与乳腺肿瘤不同临床特征的相关性.自主设计了gata3基因的引物和探针,建立检测gata3基因mRNA表达的一步法qRT-PCR检测方法,进而用建立的方法对130例临床乳腺肿瘤冰冻组织样本中gata3基因的mRNA表达进行检测,并分析gata3基因表达与乳腺肿瘤患者临床病理特征的关系.结果表明:gata3基因mRNA的相对表达量在瘤旁组织中显著高于肿瘤组织(9.1392E-02 Vs 5.0548E-02,p=0.007 1),在良性纤维腺瘤中显著高于恶性肿瘤(6.87E-02 Vs 3.42E-02,p=0.002);在乳腺浸润性导管癌中,gata3基因的表达与ER表型和Luminal分子亚型显著正相关(r_(ER表型)=0.512***;r_(分型)=0.459***);而在Luminal亚型乳腺癌样本中,gata3基因的表达与肿瘤TNM高、分化级别高显著负相关(r_(TNM分期)=-0.111*,r_(分化)=-0.147*).gata3基因异常低表达可能促进乳腺癌的发生、发展和转移,而gata3基因高表达的乳腺癌组织多伴随ER分子高表达,对内分泌药物相对敏感、预后较好.研究建立的gata3基因mRNA表达的一步法qRT-PCR检测方法可以为乳腺癌诊断和预后评估提供新的参考方法.
To analyze the mRNA expression of gata3 gene in breast tumor tissues with different pathological parameters,and explore the significance of gata3 gene expression in the diagnosis and treatment of breast cancer,NCBI platform was used to query and analyze the gata3 gene,and primers and probes of the gata3 gene were designed.Then a qRT-PCR detection method was established to analyze gata3 gene expression.The expression levels of gata3 gene in 130 samples of breast cancer frozen tissue were detected using our established methods to further analyze the relationship between gata3 gene expression and the clinic-pathological features of breast cancer patients.The results showed the relative expression of gata3 mRNA in the paraneoplastic tissues was higher than that in tumor tissues(9.1392 E-02 Vs 5.0548 E-02,p=0.007 1),and benign fibroadenomas were higher than malignant tumors(6.87 E-02 Vs 3.42 E).-02,p=0.002); in breast invasive ductal carcinoma,the expression of gata3 gene was significantly positively correlated with ER phenotype and Luminal molecular subtype(r_(ER)=0.512***; r-type=0.459***); In the Luminal subtype breast cancer samples,the expression of the gata3 gene was significantly negatively correlated with the high TNM and high differentiation levels(r_(TNM)=-0.111*,r_(differentiation)=-0.147*).The abnormal low expression of gata3 gene might be implataion in the occurrence,development and metastasis of breast cancer,while breast cancer tissues with high gata3 gene expression are highly expressed with ER molecules,relatively sensitive to endocrine drugs,and have a good prognosis.
To analyze the mRNA expression of gata3 gene in breast tumor tissues with different pathological parameters,and explore the significance of gata3 gene expression in the diagnosis and treatment of breast cancer,NCBI platform was used to query and analyze the gata3 gene,and primers and probes of the gata3 gene were designed.Then a qRT-PCR detection method was established to analyze gata3 gene expression.The expression levels of gata3 gene in 130 samples of breast cancer frozen tissue were detected using our established methods to further analyze the relationship between gata3 gene expression and the clinic-pathological features of breast cancer patients.The results showed the relative expression of gata3 mRNA in the paraneoplastic tissues was higher than that in tumor tissues(9.1392 E-02 Vs 5.0548 E-02,p=0.007 1),and benign fibroadenomas were higher than malignant tumors(6.87 E-02 Vs 3.42 E).-02,p=0.002); in breast invasive ductal carcinoma,the expression of gata3 gene was significantly positively correlated with ER phenotype and Luminal molecular subtype(r_(ER)=0.512***; r-type=0.459***); In the Luminal subtype breast cancer samples,the expression of the gata3 gene was significantly negatively correlated with the high TNM and high differentiation levels(r_(TNM)=-0.111*,r_(differentiation)=-0.147*).The abnormal low expression of gata3 gene might be implataion in the occurrence,development and metastasis of breast cancer,while breast cancer tissues with high gata3 gene expression are highly expressed with ER molecules,relatively sensitive to endocrine drugs,and have a good prognosis.
引文
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[16] Asselin Labat M L,Sutherland K D,Barker H,et al.Gata-3 is an essential regulator of mammary-gland morpho-genesis and luminal cell differentiation[J].Nat Cell Biol,2007,9(2):201-209.
[2] Chen W,Sun K,Zheng R,et al.Cancer incidence and mortality in China[J].Chinese Journal of Cancer Research,2017,29(5):11-20.
[3] Hosoda M,Yamamoto M,Nakano K,et al.Differential expression of progesterone receptor,FOXA1,GATA3,and p53 between pre-and postmenopausal women with estrogen receptor-positive breast cancer[J].Breast Cancer Research and Treatment,2014,144(2):249-261.
[4] Abba M C,Nunez M I,Colussi A G,et al.GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells[J].Breast Cancer Research,2006,8(6):R64.
[5] Jacquemier J,Charafe Jauffret E,Monville F,et al.Association of GATA3,P53,Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer[J].Breast Cancer Research,2009,11(2):R23.
[6] Mehta R J,Jain R K,Leung S,et al.FOXA1 is an independent prognostic marker for ER-positive breast cancer[J].Breast Cancer Research and Treatment,2012,131(3):881-890.
[7] Voduc D,Cheang M,Nielsen T.GATA3 expression in breast cancer has a strong association with estrogen receptor but lacks independent prognostic value[J].Cancer Epidemiology,Biomarkers & Prevention,2008,17(2):365-373.
[8] 王婷.ESR1、GATA3、GSTP1基因甲基化与人乳腺癌临床病理特征及细胞耐药关联分析[D].西安:西北大学,2017.
[9] Cakir A,Isik Gonul I,Ekinci O,et al.GATA3 expression and its relationship with clinicopathological parameters in invasive breast carcinomas[J].Pathol Res Pract,2017,213(3):227-234.
[10] Theodorou V,Stark R,Menon S,et al..GATA3 acts up-stream of FOXA1 in mediating ESR 1 binding by shaping enhanceraccessibility[J].GenomeRes,2013,23(1):12-22.
[11] Gulbahc H E,Sweeney C,Surowiecka M,et al.Significance of GATA- 3 expression in out comes of patients with breast cancer whoreceived systemic chemotherapy and/or hormonaltherapy and clini-copathologic features of GATA- 3- positive tumors[J].Hum Pathol,2013,44(11):2 427-2 431.
[12] Shaoxian T,Baohua Y,Xiaoli X,et al.Characterisation of GATA3 expression in invasive breast cancer:Differences in histological subtypes and immunohistochemically defined molecular subtypes[J].Clin Pathol.2017,70(11):926-934.
[13] Ordoez N G.Value of GATA3 immunostaining in tumor diagno-sis:A review[J].Anat Pathol,2013,20(5):352-360.
[14] Clark B Z,Beriwal S,Dabbs D J,et al.Semiquantitative GATA-3 immunoreactivity in breast,bladder,gynecologic tract,and other cytokeratin 7- positive carcinomas[J].Am J Clin Pathol,2014,142(1):64-71.
[15] Yang Y,Lu S,Zeng W,et al.GATA3 expression in clinically useful groups of breast carcinoma:A comparison with GCDFP15 and mammaglobin for identifying paired primary and metastatic tumors[J].Ann Diagn Pathol,2017,26:1-5.
[16] Asselin Labat M L,Sutherland K D,Barker H,et al.Gata-3 is an essential regulator of mammary-gland morpho-genesis and luminal cell differentiation[J].Nat Cell Biol,2007,9(2):201-209.