Expression of Hpa and CD222 in bladder carcinoma and analysis of clinico-pathologic correlation
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摘要:
目的 探讨乙酰肝素酶（HPa）及其受体CD222在膀胱癌及癌旁正常组织中的表达情况及相互作用关系，探讨其在膀胱癌发生发展中的作用及与临床、病理的关系。 方法 采用免疫组织化学SP染色法检测95例膀胱癌及20例癌旁正常组织中乙酰肝素酶和CD222的表达，并分析乙酰肝素酶和CD222的表达与膀胱癌临床病理学特征和预后的关系。 结果 1）乙酰肝素酶和CD222均表达于膀胱癌细胞浆内，阳性率分别为68.42%和61.05%，膀胱癌组织和癌旁正常组织中乙酰肝素酶的表达，及浅表性和浸润性膀胱癌组织中的表达均具有显著性差异（均P＜0.01）；2）乙酰肝素酶的表达与膀胱癌患者的肿瘤直径、病理学分级、淋巴结转移明显相关（P＜0.05），与患者年龄无统计学相关。CD222的表达与膀胱癌患者的病理学分级、淋巴结转移明显相关（P＜0.05），与患者年龄及肿瘤大小无关；3）乙酰肝素酶和CD222的表达具有显著的一致性（P＜0.05）；4）乙酰肝素酶阳性表达组患者的5年生存率低于阴性表达组，两者具有统计学差异（P＜0.05）。乙酰肝素酶与CD222共阳性表达组的5年生存率低于阴性表达组，两者具有统计学差异（P＜0.05）。 结论 乙酰肝素酶和CD222与膀胱癌转移预后密切相关，并且两者之间的表达具有相关性，可作为膀胱癌预后检测的标志物及靶向治疗研究的新靶点。 Abstract:Objective To investigate the relationships between the clinico-pathologic features and the heparanase (Hpa) and the CD222 expressions in bladder carcinoma. Methods The expressions of Hpa and CD222 in 95 bladder carcinoma specimens and 20 paraneoplastic bladder tissues (controls) were assessed using the immunohistochemical staining method. Results The positive expression rates of Hpa and CD222 in bladder carcinoma were 68.42% and 61.05%, respectively. The positive rate of Hpa was significantly higher in the carcinoma specimens than in the control specimens (P < 0.01). Similarly, the Hpa expression in the invasive bladder carcinoma was significantly higher than that in the non-invasive bladder carcinoma (P < 0.01). A positive correlation was observed between the expressions of Hpa and CD222 (P < 0.05). The expressions of Hpa and CD222 were significantly correlated with lymphatic invasion and TNM staging (P < 0.05). The negative expression of the Hpa group showed a significantly better five-year survival period than the positive expression group (P < 0.05). The co-positive expression of the Hpa group and CD222 showed a significantly worse five-year survival period compared with the non-co-positive expression group (P < 0.05). Conclusion High Hpa and CD222 expressions in tumor tissues were associated with the occurrence and development of bladder carcinoma. Results provide helpful information for the further diagnosis and therapy of cancer patients. -
Key words:
- bladder carcinoma /
- heparanase /
- CD222
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图 1 乙酰肝素酶和CD222在膀胱癌及癌旁组织中的表达（SP×400）
Figure 1. Expression of HPa and CD222 in bladder cancer and paraneo-plastic tissues
A:Negative expressoion of HPa in paraneoplastic tissue; B:Positive expression of Hpa in bladder carcinoma tissue; C:Weakly positive expression of CD222 in paraneoplastic tissue; D:Positive expression of CD222 in bladder carcinoma tissue
图 2 ROC生存曲线
Figure 2. Overall survival curves. Prognosis was significantly better in the group without Hpa expression than in the group with Hpa expression (Log-rank test, P=0.027, P < 0.05)
图 3 CD222在膀胱癌组织中的表达与生存率的关系。
Figure 3. Overall survival curves. Overall survival was not associated with CD222 expression(log-rank test, P=0.593, P>0.05)
图 4 乙酰肝素酶与CD222共阳性表达组的生存率与阴性表达组的比较
Figure 4. Overall survival curves. Overall survival rates were lower in pa-tients with co-expression of Hpa and CD222 than in patients without Hpa and CD222 expression(log-rank test, P=0.016, P < 0.05)
表 1 膀胱癌中乙酰肝素酶及CD222的表达与临床病理特征的关系
Table 1. Correlation between the clinico-pathological parameters and the expressions of Hpa and CD222
表 2 膀胱癌组织中乙酰肝素酶的表达与CD222表达的关系
Table 2. Correlation between the expressions of Hpa and CD222 in bladder carcinoma
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[1] Nargund VH, Tanabalan CK, Kabir MN, et al. Management of non-muscle-invasive (superficial) bladder cancer[J]. Semin Oncol, 2012, 39:559-572. http://www.ncbi.nlm.nih.gov/pubmed/23040252 [2] Vlodavsky I, Friedmann Y. Molecular properties and involvementof heparanase in cancer metastasis and angiogenesis[J]. J Clin Investig, 2001, 108(3):341-347. http://pubmedcentralcanada.ca/articlerender.cgi?accid=PMC209369 [3] Vlodavsky I, Eldor A., Haimovitz-Friedman, et al. Expression of heparanase by platelets and circulating cells of the immune system: possible involvement in diapedesis and extravasation[J]. Invasion Metastasis, 1992, 12(2):112-127. http://onlinelibrary.wiley.com/resolve/reference/PMED?id=1399400 [4] Pikas DS., Li JP, Vlodavsky I, et al. Substrate specificity of heparanases from human hepatoma and platelets[J]. J Biol Chem, 1998, 273(30):18770-18777. http://www.ncbi.nlm.nih.gov/pubmed/9668050 [5] Freeman C, Parish CR. Human platelet heparanase: purification, characterization and catalytic activity[J]. Biochem J, 1998, 330(Pt3): 1341-1350. http://europepmc.org/abstract/med/9494105 [6] Ilan N, Elkin M, Vlodavsky I, et al. Regulation, function and clinical significance ofheparanase incancer metastasis and angiogenesis [J]. Int J Biochem Cell Biol, 2006, 38(11):2018-2039 http://www.ncbi.nlm.nih.gov/pubmed/16901744 [7] Leksa V, Pfisterer K, Ondrovicová G, et al. Dissecting mannose 6-phosphate-insulin-like growth factor 2 receptor complexes that control activation and uptake of plasminogen in cells[J]. J Biol Chem, 2012, 287(27):22450-22462. http://search.ebscohost.com/login.aspx?direct=true&db=aph&AN=77764722&site=ehost-live [8] Harkness L, Christiansen H, Nehlin J, et al. Identification of a membrane proteomic signature for human embryonic stem cells independent of culture conditions[J]. Stem Cell Res, 2008, 1(3):219-227. http://www.sciencedirect.com/science/article/pii/S1873506108000408 [9] Thompson CA, Purushothaman A, Ramani VC, et al.Heparanase regulates secretion, composition and function of tumor cell-derived exosomes[J]. J Biol Chem, 2013, 288(10):1-11. http://ndt.oxfordjournals.org/cgi/ijlink?linkType=ABST&journalCode=jbc&resid=288/14/10093 [10] Sanderson RD, Yang Y, Kelly T, et al. J Cell Biochem. Enzymatic remodeling of heparan sulfate proteoglycans within the tumor microenvironment: growth regulation and the prospect of new cancer therapies[J]. J Cell Biochem, 2005, 96(5):897-905. http://jb.oxfordjournals.org/external-ref?access_num=10.1002/jcb.20602&link_type=DOI [11] Nilasaroya A, Martens PJ, Whitelock JM, et al. Enzymatic degradation of heparin-modified hydrogels and its effect on bioactivity[J]. Biomaterials, 2012, 33(22):5534-5540. http://test.europepmc.org/abstract/MED/22575836 [12] Leiser Y, Abu-El-Naaj I, Sabo E, et al. Prognostic value of heparanase expression and cellular localization in oral cancer[J]. Head Neck, 2011, 33(6):871-877. http://pubmedcentralcanada.ca/pmcc/articles/PMC3010289/ [13] Zheng L, Pu J, Jiang G, Weng M, et al. Abnormal expression of early growth response 1 in gastriccancer: association with tumor invasion, metastasis and heparanase transcription[J]. Pathol Int, 2010, 60 (4):268-277. http://europepmc.org/abstract/MED/20403028 [14] Gohji K, Okamoto M, Kitazawa S, et al. Heparanase protein and gene expression in bladder cancer[J]. J Urol, 2001, 166(4):1286-1290. http://www.sciencedirect.com/science/article/pii/S0022534705657540 [15] Wood RJ, Hulett MD. Cell surface expressed cation-independent mannose-6 phosphate receptor (CD222) binds enzymatically active heparanase independently of mannose-6 phosphate to promote extracellular matrix degradation[J]. J Biol Chem, 2008, 283(7): 4165-4176 http://europepmc.org/abstract/med/18073203 -
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