Expression of α-B crystalline in triple-negative breast cancer and its significance in targeted therapy
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摘要:
目的 研究a-B晶体蛋白在三阴性乳腺癌(TNBC)中的表达,通过分析a-B晶体蛋白与乳腺癌临床、病理各指标之间的相关性,从而探讨其在TNBC的预后及靶向治疗中的作用。 方法 采用免疫组织化学(IHC)S-P法检测30例TNBC,50例非TNBC的石蜡标本切片组织中的a-B晶体蛋白,比较TNBC与非TNBC组织中a-B晶体蛋白表达差异性,对a-B晶体蛋白表达与乳腺癌临床及病理指标间的关系进行相关性分析。 结果 a-B晶体蛋白在TNBC中的阳性表达率为66.67%(20/30),明显高于在非TNBC中的表达率42.00%(21/50)(χ2=4.566,P< 0.05);a-B晶体蛋白在乳腺癌中的表达与年龄、肿瘤直径、肿瘤分期无明显差异(P>0.05);与有无淋巴结转移、淋巴结转移个数、P53表达、ki-67表达有显著性差异(P< 0.05),且呈正相关。a-B晶体蛋白在TNBC中的表达与年龄、肿瘤直径、有无淋巴结转移、淋巴结转移个数、肿瘤分期、P53表达、ki-67表达无相关性(P>0.05)。 结论 a-B晶体蛋白的阳性表达在TNBC与非TNBC之间存在差异。a-B晶体蛋白在TNBC中高表达,且表达强度明显高于非TNBC。a-B晶体蛋白与乳腺癌预后不良相关,而a-B晶体蛋白在TNBC中的高表达可能为TNBC预后差的原因之一。 Abstract:Objective To investigate the expression of α-B crystalline in triple-negative breast cancer (TNBC) and discuss its role in the prognosis and targeted therapy of TNBC by analyzing the correlation among α-B crystalline and the clinico-pathological indices of breast cancer. Methods Immunohistochemistry SP assay was used to determine α-B crystalline expression in paraffin-embedded specimens of 30 cases of TNBC and 50 cases of non-TNBC tissues. The differences in protein expressions among tissues were compared, and correlation analysis was performed to determine the relationship between protein expression and clinico-pathological indices. Results The positive expression rate of α-B crystalline was 66.67% in TNBC (20/30) and 42.00% in non-TNBC (21/50), which indicates that the expression is significantly higher in TNBC than in the non-TNBC tissues (χ 2=4.566, P< 0.05). The expression of α-B crystalline in breast cancer has no significant difference in terms of age, tumor diameter, and cancer stage (P>0.05), but exhibits a difference in terms of lymph node metastasis and the number of metastasized lymph nodes [P53, Ki67 (P< 0.05)], which presents a positive correlation (r=0.251). The α-B crystalline expression in TNBC has no significant difference among indices such as age, tumor diameter, nodal metastasis, number of metastasis, P53, cancer stage, and Ki67 (P>0.05). Conclusion Significant differences were found in α-B crystalline expression between TNBC and non-TNBC. α-B crystalline is highly expressed in TNBC tissues, and the expression is significantly higher in TNBC tissues than that in non-TNBC tissues. α-B crystalline is associated with poor prognosis of breast cancer. Consequently, the overexpression of α-B crystalline in TNBC may be a reason for unfavorable TNBC prognosis. -
表 1 a-B晶体蛋白在不同乳腺癌组织中的表达 例
Table 1. Expression of α-B crystalline in different breast cancer (n)
表 2 不同乳腺癌组织中a-B晶体蛋白免疫组化评分的比较
Table 2. Comparison of IHS scores
表 3 a-B晶体蛋白的表达与乳腺癌临床、病理指标间的相关性 例
Table 3. Correlation of α-B crystalline expression in breast cancer with clinicopathologic features and tumor markers of patients (n)
表 4 a-B晶体蛋白的表达与三阴性乳腺癌临床、病理指标间的相关性 例
Table 4. Correlation of α-B crystalline expression in TNBC with clinicopathologic features and tumor markers of patients (n)
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[1] Bauer KR, Brown M, Cress RD, et al. Descriptive analysis of estrogen receptor(ER)-negative, progesterone receptor(PR)-negative, and HER-2 negative invasive breast cancer, the SO·-called triple-negative phenotype: Apopulation-based study from the Califomia Cancer Registry[J]. Cancer, 2007, 109(9): 1721-1728. doi: 10.1002/cncr.22618 [2] Dabir DV, Trojanowski JQ, Richter-Landsberg G, et al. Expression of the small heat-shock protein alphaB-crystalline in tauopathies with glial pathology[J]. Am J Pathol, 2004, 164(1): 155-166. doi: 10.1016/S0002-9440(10)63106-9 [3] Arrigo S, Simon B, Giber C, et al. Hsp27(HspB 1)and aB-crystallin(HspB5) as therapeutic targets[J]. FEBS Letters, 2007, 581(19): 3665-3674. doi: 10.1016/j.febslet.2007.04.033 [4] Moyano IV, Evans JR, Chen F, et al. a-B crystalline is a novel oncoprotein that predicts poor clinical outcome in breast cancer[J]. J Clin Invest, 2006, 116(1): 261-270. [5] Soslow RA, Dannenberg AJ, Rush D, et al. Cox-2 is expressed in human pulmonary, colonic, and mammary tumors[J]. Cancer, 2000, 89: 2637-2645. doi: 10.1002/1097-0142(20001215)89:12<2637::AID-CNCR17>3.0.CO;2-B [6] Bryan BB, Schnitt SJ, Colins LC, et al. Ductalcarcinoma insitu with basal-like phenotype: a possible precursor toinvasive basal-like breast cancer[J]. Mod Pathol, 2006, 19(5): 617-621. doi: 10.1038/modpathol.3800570 [7] Goldhirsch A, Wood WC, Coates AS, et al. Strategies for sub-types-dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consens us on the Primary The rapy of Early Breast Cancer 2011[J]. Ann Oncol, 2011, 22(8): 1736-1747. doi: 10.1093/annonc/mdr304 [8] 张保宁, 张慧明. 三阴性乳腺癌研究进展: 第31届圣安东尼奥乳腺癌研讨会报道[J/CD ]中华乳腺病杂志(电子版), 2009, 3(1): 5-8. [9] Dennison SK, Jacobs SA, Wilson JW, et al. A phaseⅡ clinical trial of ZD1839(Iressa)in combination with docetaxel as first line treatment in patients with advanced breast cancer[J]. Invest New Drugs, 2007, 25(6): 545-551. doi: 10.1007/s10637-007-9055-6 [10] 刘双, 肖献忠. aB晶体蛋白的功能与疾病[J]. 生命的化学, 2005, 25 (2): 19-21. https://www.cnki.com.cn/Article/CJFDTOTAL-SMHX200502003.htm [11] Li DW, Xiang H, Mao YW, et al. Caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis[J]. Exp Cell Res, 2001, 266(2): 279-291. doi: 10.1006/excr.2001.5223 [12] Kamradt MC, Chen F, Sam S, et al. The small heat shock protein al. phaB-crystallin negatively regulates apoptosis during myogenic differentiation by inhibiting caspase-3 activation[J]. J Biol Chem, 2002, 277(41): 543-549. [13] Kim HS, Lee Y, Lim YA, et al. aB- crystalline is a Novel Oncoprotein Associated with Poor Prognosis in Breast Cancer[J]. J Breast Cancer, 2011, 14(1): 14-19. doi: 10.4048/jbc.2011.14.1.14 [14] 房爱菊, 高永生, 李盛梅, 等. 转移相关蛋白与乳腺癌转移潜能的相关性分析[J]. 中国普通外科杂志, 2008, 17(11): 1079-1083. https://www.cnki.com.cn/Article/CJFDTOTAL-ZPWZ200811013.htm [15] Chelouche-Lev D, Kluger HM, Berger AJ, et al. a-B crystalline as a marker of lymph node involvement in breast carcinoma[J]. Cancer, 2004, 100(12): 2543-2548.