摘要
目的:
探讨p97在骨肉瘤组织中的表达情况及是否可能参与骨肉瘤的远处转移。
方法:
采用免疫组织化学(MaxVisionTM)检测60例普通型骨肉瘤组织p97的表达情况,21例骨软骨瘤组织作为对照。以肿瘤与正常组织交界处的血管内皮细胞作为内参。结合临床资料,判断p97表达与骨肉瘤远处转移病例之间的关系。
结果:
60例普通型骨肉瘤组织中p97阴性表达34例,阳性表达26例;21例骨软骨瘤组织中p97阴性表达20例,阳性表达1例,二者统计学差异明显(P= 0.001)。14例发生远处转移的骨肉瘤组织中p97阴性表达3例,阳性表达11例;46例无远处转移的骨肉瘤组织中p97阴性表达31例,阳性表达15例,二者统计学差异显著(P=0.002)。
结论:
p97可能参与了骨肉瘤发生与远处转移。提示p97检测可能成为判断骨肉瘤发生远处转移的一项有价值的指标;同时P97为骨肉瘤的诊疗提供一种新的可能分子靶标和途径。
Objective: To evaluate the expression of p97 in osteosarcoma and its correlation with distant metastasis.
Methods 60 cases of general osteosarcoma obtained at surgery were fixed in 10% formalin and routinely processed for paraffin embedding. Immunohistochemical analysis was applied to detect the expression of P97 in human osteosarcoma histocyte including 13 cases with lung metastasis and 1 case with oral metastasis. 21 cases of osteoenchondroma samples tissue were detected for control.And the staining intensity of P97 in the normal noncancerous tissue for internal standard.
Result Immunohistochemical staining of p97 was buffy, and the p97was located in cytoplasm. The positive expression rate of p97 was 43.3% in osteosarcoma and 4.8% in osteoenchondroma respectively.p97 expression was significantly higher in osteosarcoma than in osteoenchondroma (p=0.01), though it was not correlated with histological type of osteosarcoma. There were 11cases with p97 positive exprssion in the 14 cases with distant metastasis. The positive expression rate (11/14, 78.6%)was significantly higher in the cases with distant metastasis than those without metastasis(15/46, 32.6%).
Conclusion p97 may be involved in the development, progression and metastasis of osteosarcoma. And p97 can be a new diagnostic and therapeutic target for osteosarcoma.
引文
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[1]赵劲松,黄岚峰,张延哲.鸡VCP蛋白全长cDNA的克隆及序列分析.中国实验诊断学,2008;429-432
[2] Wang Q, Song C,Yang X,Li CC.D1 ring is stable and nucleotide—independent.whereas D2 ring underProes major conformational changes during the ATPase cycleof p97一vcp.Biol Chem 2003;278:32784—32793
[3] RouilIer I,DeLaBaHe B,May AP,Weis WI,Brunger AT,Mil1igan RA,Wilson-Kubalek EM.Conformational changes of the multifunction p97 AAA ATPase during its ATPase cycIe.Nat struct Biol 2002;9:950.957
[4] inion FC ,Adams C ,HsuT.R1 region of P97 mediates adherence of Mycoplasma hyopneumoniae to swine cilia [J].Infect Immun ,2002,68(5):3056.
[5] Patel S Latterich M .The AAA team;related ATPases diverse functions.Trends[J].cell Biol ,1998,8(2):65
[6] Hemmo H,Meyer,James G,Shorter,Joachim seemann,Darry Pappin,Graham Warren.A complex of mammalian Ufdl and Npl4 links the AAA-ATPase,p97,to ubiquitin and nuclear transport pathways.EABO 2000;10:2181-2192
[7] Uchiyama K,Jokitalo E,Lindman M,Jackman M,Kano F,Murata M,Zhang X,Kondo H .The localization and phosphorylation of p47 are important for GoIgi disassembly- assembIy during the cell cycle.J cell Biol 2003;161:1067—1079
[8] Zhang SH,Liu J,Kobayashi R,Tonks NK.Identification of the cell cycle regulator VCP(p97/cDc48)as a substrate of the band 4.1-related protein-tyrosine phosphatase PTPHl.J Biol Chem 1999;274:17806-17812
[9] Huyton T,Pye VE,Briggs LC,Flynn TC,Beuron F,Kondo H, Ma J,Zhang X,Freemont PS.The crystal structure of murine p97/VCP at 3.6A.J Struct Biol 2003;144:337-348
[10] Egerton M,Ashe OR,Chen D,Druker BJ,Burgess WH,Samelson LE.VCP,the mammalian homolog of cdc48,is tyrosine phosphorylated in response to T ceIl antigen receptor activation.EMBO J 1992;11:3533—3540
[11] Hirabayashi M,Inoue K Tanaka K,Nakadate K,ohsawa Y, Kamei Y,Popiel AH,Sinohara A,Iwamatsu A,Kimura Y, Uchiyama Y,Hori S,Kakizuka A.VCP/p97 in abnormaI protein aggregates,cytoplasmic vacuo1es,and cell death,phenotypes relevant to neuro degeneration.Cell Death Differ 2001; 8: 977-984
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[20] Lacasse EC,Baird S,Korneluk RG, et al.he inhibitors of apoptosis (IAP) and their emerging role in cancer [J ].Oncogene,1998,17:3247
[21] Alexandru G,Graumann J,Smith GT,et al.UBXD7 binds mltiple ubiquitin ligases and implicates P97 in HIF1alpha turnover.Cell 2008;134:804-816
[22] Dipersio CM ,Shao M,Di-Costanzo L, et al.Mouse keratinocytes immortalized with large T antigen acquire alpha 3 beta 1 integrin dependent secretion of MMP9/gelatinase B [J ].J Cell Sci,2000,113(Pt16):2909-2921
[23] Asai T,Tomita Y,Nakatsuka S,et al.VCP(p97)regulates NF-κB signaling pathway, which is important formetastasis of Osteosarcoma cell line [J].Jpn J Cancer Res,2002,93(3):296 - 304.
[24] Yamamoto S,Tomita Y,Hoshida Y,Iizuka N,Kidogami S,Miyata H,Takiguchi S,Fujiwara Y,Yasuda T,Yano M,Nakamori S,Sakon M,Monden M,Aozasa K.Expression level of valosin-containing protein(p97)is associated with prognosis of esophageal carcinoma.Clinic Cancer Res 2004;10:5558—5565
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[29] Wang ZH,Shen D,Williams P,Alberto B,Jason S,Steve S,Janine P,Natalie S,Brock A.Mutational analysis of the tyrosine phosphatome in colorectal cancers.Science 2004;304:1164—1166
[30]裘莹,宋伯根,王军臣等.VCP蛋白表达与胃癌预后的相关性研究.肿瘤,2006;10:935-940
[31]游燊,王志明,何晓顺,周乐杜.VCP在肝细胞癌中的表达及临床意义.中国普通外科杂志,2007,16(8):813-816.
[32] Yamamoto S,Tomita Y,Hoshida Y,Iizuka N,Monden M,Yamamoto S,Iuchi K,Aozasa K.Expression level of valosin containing protein(P97)is correIated with Progression and prognosis of non—small—cell 1ung carcinoma.Ann surg Oncol 2004;11:697.704
[33] Tsujimoto Y,Tomita Y,Hoshida Y,Kono T,Oka T,Yamamoto S,Nonomura N,Okuyama A,Aozasa K.E1evated expression of valosin一containing protein(p97)is associated with poor prognosis of prostate cancer. Clin Cancer Res 2004;10:3007-3012
[34] Yamamoto S,Tomita Y,Hoshida Y,Toyosawa S,Inohara H,Kishino M,Kogo M,Nakazawa M,Murakami S,Iizuka N,Kidogami S,Monden M,Kubo T,Ijuhin N,Aozasa K.Expression level of Valosin containing protein(VcP)as a prognostic marker for gingival squamous cell carcinoma.Ann Oncol 2004;15:1432-1438
[35]杨兆红,张克君.非小细胞肺癌中p97蛋白的表达及其临床意义.医学创新研究,2006;3(2):1-4