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淋巴结转移乳腺癌患者中RARβ基因甲基化的预后判断价值

李少英, 李 荣, 麦慧芬, 王 维, 吴华聪, 陈 静, 罗荣城

李少英, 李 荣, 麦慧芬, 王 维, 吴华聪, 陈 静, 罗荣城. 淋巴结转移乳腺癌患者中RARβ基因甲基化的预后判断价值[J]. 肿瘤防治研究, 2014, 41(05): 443-446. DOI: 10.3971/j.issn.1000-8578.2014.05.022
引用本文: 李少英, 李 荣, 麦慧芬, 王 维, 吴华聪, 陈 静, 罗荣城. 淋巴结转移乳腺癌患者中RARβ基因甲基化的预后判断价值[J]. 肿瘤防治研究, 2014, 41(05): 443-446. DOI: 10.3971/j.issn.1000-8578.2014.05.022
LI Shaoying, LI Rong, MAI Huifen, WANG Wei, WU Huacong, CHEN Jing, LUO Rongcheng. RARβ Gene Methylation Could Be Used in Prognosis of Breast Cancer Patients with Lymphatic Metastasis[J]. Cancer Research on Prevention and Treatment, 2014, 41(05): 443-446. DOI: 10.3971/j.issn.1000-8578.2014.05.022
Citation: LI Shaoying, LI Rong, MAI Huifen, WANG Wei, WU Huacong, CHEN Jing, LUO Rongcheng. RARβ Gene Methylation Could Be Used in Prognosis of Breast Cancer Patients with Lymphatic Metastasis[J]. Cancer Research on Prevention and Treatment, 2014, 41(05): 443-446. DOI: 10.3971/j.issn.1000-8578.2014.05.022

淋巴结转移乳腺癌患者中RARβ基因甲基化的预后判断价值

详细信息
    作者简介:

    李少英(1980-),女,硕士,主治医师,研究方向为肿瘤学

    通讯作者:

    罗荣城,E-mail:luorc01@163.com;张军,E-mail:zhangjy@163.com

  • 中图分类号: R737.9;R730.7

RARβ Gene Methylation Could Be Used in Prognosis of Breast Cancer Patients with Lymphatic Metastasis

  • 摘要: 目的 探讨视黄醇受体(RAR??β基因的DNA甲基化在乳腺癌发生发展过程中的意义。方法采用特异性MSP方法,检测乳腺癌和正常乳腺组织中RARβ基因的DNA甲基化状态,并结合其临床病理特性和预后进行分析。结果 192例乳腺癌组织中RARβ基因甲基化者50例(26%),而在正常乳腺组织中无一例甲基化,甲基化率与患者的肿瘤组织学类型、分期和肿瘤大小有相关性(P<0.05);淋巴结转移、ER阴性及HER2过度表达的癌组织中RARβ基因甲基化率增高,但无统计学意义。RARβ基因甲基化的乳腺癌患者的生存率低(P=0.268), 尤其是淋巴结转移的乳腺癌患者(P=0.040)。结论 RARβ基因甲基化在乳腺癌的发生、发展中起着重要作用,可能与乳腺癌的侵袭性密切相关,可作为判断淋巴结转移的乳腺癌预后的分子生物学指标。

     

    Abstract: Objective To determine the roles of retionoic acid receptor β(RARβ) gene methylation in the occurrence and development of breast cancer. Methods We screened the primary human breast tumors and normal breast tissues for RARβ gene promoter methylation by methylation specify PCR(MSP), and the results were analyzed together with corresponding clinical pathological data. Results The frequency of RARβ gene methylation in 192 cases was 26% (50/192), however no RARβ gene methylation was found in normal breast tissues. RARβ methylation were associated with tumor histological type, staging and tumor size (P<0.05). Patients with lymph node metastasis, ER(-)and HER2 amplified had more RARβmethylation(P>0.05). Patients with RARβ methylation had low survival rate(P=0.268), particularly those combined with lymphatic metastasis (P=0.04). Conclusion RARβ gene promoter methylation may play an important role in the carcinogenesis and development of breast cancer. The relationship with poor differentiation, large tumor size and poor survival rate indicates that RARβ methylation could be used in the prognosis of breast cancer patients with lymphatic metastasis.

     

  • [1] Anothaisintawee T, Teerawattananon Y, Wiratkapun C, et al. Risk prediction models of breast cancer: a systematic review of model performances[J]. Breast Cancer Res Treat,2012,133 (1):1-10.
    [2] Zhu W, Qin W, Hewett JE, et al. Quantitative evaluation of DNA hypermethylation in malignant and benign breast tissue and fl uids[J]. Int J Cancer,2010, 126(2):474-82.
    [3] Cho KW, Kwon HJ, Shin JO, et al. Retinoic acid signaling and the initiation of mammary gland development[J]. Dev Biol,2012, 365 (1) :259-66.
    [4] Salazar MD, Ratnam M, Patki M, et al. During hormone depletion or tamoxifen treatment of breast cancer cells the estrogen receptor apoprotein supports cell cycling through the retinoic acid receptor alpha1 apoprotein[J]. Breast Cancer Res,2011,13(1):R18.
    [5] Herman JG, Graff JR, Myöhänen S, et al. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands[J]. Proc Natl Acad Sci U S A,1996,93 (18): 9821-6.
    [6] Paulin R, Grigg GW, Davey MW, et al. Urea improves efficiency of bisulphate-mediated sequencing of 5’-methylcytosine in genomic DNA[J]. Nucleic Acids Res,1998, 26 (21): 5009-10.
    [7] Zlobec I, Bihl M, Foerster A, et al. Comprehensive analysis of CpG island methylator phenotype (CIMP)-high, -low, and -negative colorectal cancers based on protein marker expression and molecular features[J]. J Pathol,2011, 225(3):336-43.
    [8] Soong R, Iacopetta BJ, Harvey JM, et al. Detection of p53 gene mutation by rapid PCR-SSCP and its association with poor survival in breast cancer[J]. Int J Cancer,1997, 74 (6): 642-7.
    [9] Lee X, Si SP, Tsou HC, et al. Cellular aging and transformation suppression: a role for retinoic acid receptor beta 2[J]. Exp Cell Res, 1995, 218 (1):296-304.
    [10] Sun J, Xu X, Liu J, et al. Epigenetic regulation of retinoic acid receptorβ2 gene in the initiation of breast cancer[J]. Med Oncol, 20 11, 28(4):1311-8.
    [11] Lewis CM, Cler LR, Bu DW, et al. Promoter hypermethylation in benign breast epithelium in relation to predicted breast cancer risk[J]. Clin Cancer Res, 2005, 11(1):166-72.
    [12] Yang Q, Mori I, Shan L, et al. Biallelic inactivattion of retinoic acid receptor beta2 gene by epigenetic change in breast cancer[J]. Am J Pathol, 2001,158(1):299-303.
    [13] Yan PS, Perry MR, Laux DE, et al. CpG island arrays: an application toward deciphering epigenetic signatures of breast cancer[J]. Clin Cancer Res, 2000, 6(4): 1432-8.
    [14] Nass SJ, Herman JG, Gabrielson E, et al. Aberrant methylation of the estrogen receptor and E-cadherin 5’CpG islands increases with malignant progression in human breast cancer[J]. Cancer Res, 2000 ,60 (16): 4346-8.
    [15] Toyota M, Ahuja N, Ohe-Toyota M, et al. CpG island methylator phenotype in colorectal cancer[J]. Proc Natl Acad Sci U S A, 19 99, 96 (15): 8681-6.
    [16] Hawkins N, Norrie M, Cheong K, et al. CpG island methylation in sporadic colorectal cancers and its relationship to microsatellite instability[J]. Gastroenterology, 2002, 122 (5): 1376-87.
    [17] van Rijnsoever M, Grieu F, Elsaleh H, et al. Characterisation of colorectal cancers showing hypermethylation at multiple CpG islands[J]. Gut, 2002, 51 (6):797-802.
    [18] Fackler MJ, McVeigh M, Evron E, et al. DNA methylation of RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist in in situ and invasive lobular breast carcinoma[J]. Int J Cancer, 2003, 107(6): 970-5.
    [19] Yang X, Yan L, Davidson NE. DNA methylation in breast cancer[J]. Endocr Relat Cancer, 2001, 8 (2): 115-27.
    [20] Mehrotra J, Ganpat MM, Kanaan Y, et al. Estrogen receptor/ progesterone receptor-negative breast cancers of young African- American women have a higher frequency of methylation of multiple genes than those of Caucasian women[J]. Clin Cancer Res, 2004, 10 (6): 2052-7.
    [21] Widschwendter M, Siegmund KD, Müller HM, et al. Association of breast cancer DNA methylation profiles with hormone receptor status and response to tamoxifen[J]. Cancer Res,2004,64 (11):3807-13.
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出版历程
  • 收稿日期:  2013-06-09
  • 修回日期:  2013-10-29
  • 刊出日期:  2014-05-24

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