BAG-1, EGFR, and PARP-1 expressions in breast cancer and their clinical significance
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摘要:
目的 观察乳腺癌组织芯片中BAG-1、EGFR和PARP-1的表达及其与临床病理指标的相关性,并探讨其临床意义。 方法 采用免疫组织化学法对159例组织芯片中乳腺癌和癌旁组织点行BAG-l、EGFR及PARP-1蛋白检测,同时分析其与临床病理指标的相关性。 结果 乳腺癌组织中BAG-1、EGFR、PARP-1蛋白表达水平显著高于癌旁组织(P < 0.05)。BAG-1蛋白表达水平与年龄、肿瘤部位、淋巴结转移数目、临床分期均无明显相关性,但与肿瘤大小、组织学分级、ER、PR和HER-2表达以及分子分型有关(P < 0.05);EGFR蛋白表达水平与肿瘤大小、临床分期以及分子分型有明显相关性(P < 0.05);PARP-1与组织学分级、淋巴结转移数目、ER表达以及分子分型有关(P < 0.05)。119例病例中BAG-1蛋白表达与EGFR、PARP-1蛋白表达无明显相关性,但在三阴性乳腺癌(TNBC)中BAG-1蛋白表达与PARP-1蛋白表达呈正相关(P < 0.05)。单因素分析结果显示,BAG-1、PARP-1蛋白表达和分子分型是影响乳腺癌患者预后的因素。多因素分析结果显示,BAG-1、PARP-1蛋白表达是影响乳腺癌患者预后的独立危险因素。 结论 乳腺癌中BAG-1、EGFR和PARP-1蛋白高表达提示其可能参与乳腺癌的发生发展,BAG-1、EGFR和PARP-1高表达可作为乳腺癌诊治和预后的生物指标。 -
关键词:
- 乳腺癌 /
- 免疫组织化学 /
- BAG-1 /
- 表皮生长因子受体 /
- 聚ADP核糖聚合酶-1
Abstract:Objective To observe BAG-1, EGFR, and PARP-1 expressions in invasive breast cancer and its correlation with clinical pathological indicators, as well as to evaluate their clinical significance. Methods The BAG-l, EGFR, and PARP-1 expressions in a tissue microarray of invasive breast cancer and peritumoral tissues were detected through immunohistochemical staining. The clinical and pathological significance of BAG-1, EGFR, and PARP-1 were evaluated. Results The BAG-1, EGFR, and PARP-1 expression levels are higher in invasive breast cancer tissues than in peritumoral tissues (P < 0.05). BAG-1 expression in invasive cancer tissues is not related to age, tumor site, lymph node metastases, and clinical TNM staging of patients, but is related to size, grade, ER, PR, and HER-2 expressions and molecular subtype (P < 0.05). EGFR expression is related to size, clinical TNM staging, and molecular subtype (P < 0.05). PARP-1 expression is related to grade, lymph node metastases, ER, and molecular subtype (P < 0.05). BAG-1 expression is not significantly correlated with EGFR and PARP-1 in all cases, but BAG-1 and PARP-1 expressions are positively correlated in triple-negative breast cancer tissues (P < 0.05). Results of the univariate analysis revealed that the BAG-1 and PARP-1 expressions and the molecular subtypes are associated with the prognoses of breast cancer patients. Multivariate analysis revealed that BAG-1 and PARP-1 expressions are factors that are independent of the prognosis. Conclusion BAG-1, EGFR, and PARP-1 overexpressions in human breast tissues suggest that BAG-1, EGFR, and PARP-1 are related to breast cancer development. BAG-1, EGFR, and PARP-1 are potential biomarkers of breast cancer diagnosis and prognosis. -
表 1 BAG-1、EGFR和PARP-1表达与临床病理指标的关系 例(%)
Table 1. Relationship of BAG-1, EGFR, and PARP-1 expression with clinico pathologic indicators n (%)
表 2 影响乳腺癌患者预后的单因素分析
Table 2. Correlation of various indicators with overall survival(OS)in breast cancer
表 3 影响乳腺癌患者预后的多因素分析
Table 3. Multivariate analysis of prognostic factors in breast cancer
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[1] Redig AJ, McAllister SS. Breast cancer as a systemic disease: a view of metastasis[J]. J Intern Med, 2013, 274(2):113-126. http://old.med.wanfangdata.com.cn/viewHTMLEn/PeriodicalPaper_PM23844915.aspx [2] Anders CK, Deal AM, Miller CR, et al. The prognostic contribution of clinical breast cancer subtype, age, and race among patients with breast cancer brain metastases[J]. Cancer, 2011, 117(8):1602-1611. doi: 10.1002/cncr.25746 [3] Leng XF, Chen MW, Xian L, et al. Combined analysis of mRNA expression of ERCC1, BAG-1, BRCA1, RRM1 and TUBB3 to predict prognosis in patients with non-small cell lung cancer who received adjuvant chemotherapy[J]. J Exp Clin Cancer Res, 2012, 31:25. doi: 10.1186/1756-9966-31-25 [4] Guo P, Huang ZL, Yu P, et al. Trends in cancer mortality in China: an update[J]. Ann Oncol, 2012, 23(10):2755-2762. doi: 10.1093/annonc/mds069 [5] Cutress RI, Townsend PA, Brimmell M, et al. BAG-1 expression and function in human cancer[J]. Br J Cancer, 2002, 87(8):834-839. doi: 10.1038/sj.bjc.6600538 [6] Liu H, Lu S, Gu L, et al. Modulation of BAG-1 Eexpression alters the sensitivity of breast cancer cells to tamoxifen[J]. Cell Physiol Biochem, 2014, 33(2):365-374. http://europepmc.org/abstract/med/24557447 [7] Knapp RT, Wong MJ, Kollmannsberger LK, et al. Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function[J]. PLoS One, 2014, 9(1):e85415. doi: 10.1371/journal.pone.0085415 [8] Townsend PA, Dublin E, Hart IR, et al. BAG-1 expression in human breast cancer: interrelationship between BAG-1 RNA, protein, HSC70 expression and clinical-pathological data[J]. J Pathol, 2002, 197(1):51-59. doi: 10.1002/path.1081/abstract [9] Nadler Y, Camp RL, Giltnane JM, et al. Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer[J]. Breast Cancer Res, 2008, 10(2):R35. doi: 10.1186/bcr1998 [10] Ni W, Chen B, Zhou G, et al. Overexpressed nuclear BAG‐1 in human hepatocellular carcinoma is associated with poor prognosis and resistance to doxorubicin[J]. J Cell Biochem, 2013, 114(9):2120-2130. doi: 10.1002/jcb.24560 [11] Leite MS, Giacomin LC, Piranda DN, et al. Epidermal growth factor receptor gene polymorphisms are associated with prognostic features of breast cancer[J]. BMC Cancer, 2014, 14:190. doi: 10.1186/1471-2407-14-190 [12] Rakha EA, El‐Sayed ME, Green AR, et al. Prognostic markers in triple-negative breast cancer[J]. Cancer, 2007, 109(1):25-32. http://cn.bing.com/academic/profile?id=915436d07b3ed1aace03292b119382cd&encoded=0&v=paper_preview&mkt=zh-cn [13] Domagala P, Huzarski T, Lubinski J, et al. PARP-1 expression in breast cancer including BRCA1-associated, triple negative and basal-like tumors: possible implications for PARP-1 inhibitor therapy [J]. Breast Cancer Res Treat, 2011, 127(3):861-869. doi: 10.1007/s10549-011-1441-2 [14] Rojo F, García-Parra J, Zazo S, et al. Nuclear PARP-1 protein overexpression is associated with poor overall survival in early breast cancer[J]. Ann Oncol, 2012, 23(5):1156-1164. doi: 10.1093/annonc/mdr361 [15] Southern SL, Collard TJ, Urban BC, et al. BAG-1 interacts with the p50-p50 homodimeric NF-κ B complex: implications for colorectal carcinogenesis[J]. Oncogene, 2012, 31(22):2761-2772. doi: 10.1038/onc.2011.452