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内质网分子伴侣GRP78在乳腺癌中的表达及其预后意义 被引量:3

Expression of endoplasmic reticulum chaperone GRP78 in breast cancer and its prognosis significance
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摘要 目的探讨乳腺癌中GRP78的表达及其与乳腺癌临床、病理特征的相关性及其预后意义。方法采用免疫组化Envision法检测了172例乳腺癌石蜡标本中GRP78的表达并对其表达与乳腺癌患者的月经状况、肿瘤大小、淋巴结转移状况、病理类型、组织学分级、激素受体状况、Her-2、Ki-67表达状况等临床、病理特征的相关性以及与预后的关系进行统计分析。结果在172例手术切除的乳腺癌标本中,GRP78普遍阳性表达于肿瘤细胞,其中71例(41.28%)为强表达,101例(58.72%)为弱表达。GRP78的表达与乳腺癌患者的月经状况、淋巴结转移状况、病理类型、组织学分级、激素受体状况、Ki-67表达状况等临床、病理特征无相关性(P〉0.05);其在T3、Her-2阳性乳腺癌患者中的表达显著高于在T1、T2和Her-2阴性患者中的表达(P〈0.05)。生存分析结果表明,GRP78强表达患者的无病生存时间和总生存时间较弱表达患者差,差异有统计学意义(P〈0.05)。Cox回归分析表明,GRP78的表达状况是乳腺癌患者无病生存时间的独立预后因素(P〈0.05),但不是总生存时间的独立预后因素(P〉0.05)。结论GRP78普遍阳性表达于乳腺癌,其表达增强,预示患者预后不良,GRP78的表达状况对判断乳腺癌患者的预后具有一定的参考价值。 Objective To investigate the expression of GRP78 in breast cancer, the relationships among the expression and the clinicopathological characteristics, prognosis were also investigated. Methods The expression of GRP78 was detected in 172 paraffin-embedded breast cancer samples with immunohistochemis- try Envision method, the relationships among the expression and the clinicopathological characteristics, prog- nosis were investigated. Results Positive expression of GRP78 is common in breast cancer. Strong expres- sion of GRP78 was detected in 71 cases (41.28%) , and weak expression was detected in 101 cases (58. 72% ). GRP78 expression wasn't associated with the clinicopathological characterristics except T stage and Her-2 status. Univariate analysis (log-rank test) showed that GRP78 expression correlated with disease free survival and overall survival significantly. Patients with strong GRP78 expression had poorer prognosis com- pared to those with weak GRP78 expression( P 〈 0.05 ). Multivariate analysis utilizing Cox regression analy- sis showed that GRP78 is an independent biomarker of disease free survival ( P 〈 0.05 ) , but not an inde- pendent biomarker of overall survival (P 〉 0.05). Conclusions Positive expression of GRP78 is common in breast cancer and strong expression is associated with poorer survival.
出处 《国际外科学杂志》 2016年第3期157-162,F0003,共7页 International Journal of Surgery
关键词 GRP78蛋白 乳腺肿瘤 预后 GRP78 protein, human Breast neoplasms Prognosis
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  • 1Luo B, Lee AS. The critical roles of endoplasmic reticulum chaper- ones and unfolded protein response in tumorigenesis and anticancer therapies [J]. Oncogene, 2013, 32 (7): 805-818. DOI:10. 1038/onc. 2012. 130.
  • 2Reddy RK, Mao C, Banmeister P, et al. Endoplasmic retieulum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors: role of ATP binding site in suppression of caspase-7 activation[J]. J Biol Chem, 2003, 278 (23) : 20915- 20924. DOI:I0. 1074/jbc. M212328200.
  • 3Fu Y, Li J, Lee AS. GRP'/8/BiP inhibits endoplasmic reticulum BIK and protects human breast cancer ceils against estrogen-starva- tion induced apoptosis ~ J]. Cancer Res, 2007, 67 (8) : 3734- 3740. DOI: 10.1158/0008-5472. CAN-06-4594.
  • 4Wu MJ, Jan CI, Tsay YG, et al. Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling [J~. Mol Cancer, 2010, 9: 283. DOI:10. 1186/1476- 4598-9-283.
  • 5Bartkowiak K, Effenberger KE, Harder S, et al. Discovery of a no- vel unfolded pro-tein response phenotype of cancer stem/progenitor cells from the bone marrow of breast cancer patients [ J ]. J Proteome Res, 2010, 9(6) : 3158-3168. DOI:IO. 1021/pr 100039d.
  • 6Dong D, Ni M, Li J, et al. Critical role of the stress chaperone GRP78/BiP in tumor proliferation, survival, and tumor angiogene- sis in transgene-induced mammary tumor development[ J 1. Cancer Res, 2008, 68 ( 2 ) : 498-505. DOI: 10. 1158/0008-5472. CAN- 07-2950.
  • 7Dong D, Stapleton C, Luo B, et al. A critical role for GRP78/BiP in the tumor microenvironment for neovascularization during tumor growth and metastasis [ J ]. Cancer Res, 2011, 71 ( 8 ) : 2848- 2857. DOI:I0. 1158/0008-5472. CAN-10-3151.
  • 8Katanasaka Y, Ishii T, Asai T, et al. Cancer antineovascular ther- apy with liposome drug delivery systems targeted to BiP/GRP78 [J]. Int J Cancer, 2010, 127(11) : 2685-2698. DOI:I0. 1002/ ijc. 25276.
  • 9Kern J, Untergasser G, Zenzmaier C, et al. GRP-78 secreted by tumor ceils blocks the antiangiogenic activity of bortezomib [ J ]. Blood, 2009, 114 ( 18 ) : 3960-3967. DOI : 10.1182/blood-2009- 03-209668.
  • 10Dong D, Dubean L, Bading J, et al. Spontaneous and controllable activation of suicide gene expression driven by the stress-inducible grp78 promoter resulting in eradication of sizable human tumors [Jl. Hum Gene Ther, 2004, 15(6) : 553-561. DOI: lO. 1089/ 104303404323142006.

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