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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

ASPM预测不良的临床结果并促进弥漫性大型B细胞淋巴瘤的肿瘤发生。

卷 21, 期 1, 2021

发表于: 15 September, 2020

页: [80 - 89] 页: 10

弟呕挨: 10.2174/1568009620666200915090703

价格: $65

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摘要

背景：异常的纺锤状小头畸形相关蛋白（ASPM）已被认为与几种恶性肿瘤的侵袭行为有关。然而，其对弥漫性大B细胞淋巴瘤（DLBCL）的潜在影响仍然未知。 方法：采用免疫组织化学方法测定54例DLBCL组织和15例反应性淋巴样增生组织（RLH）的ASPM水平，并评估其与临床特征和总生存率的关系。评估了ASPM对DLBCL细胞的生长，细胞凋亡和细胞周期的影响。进行了生物信息学，定量RT-PCR和Western blotting的力学研究。 结果：与RLH组织相比，DLBCL组织中ASPM表达上调。其高表达与DLBCL患者的临床病理特征较差和预后不良有关。多变量分析表明，ASPM的高表达是预后不良的独立因素。在DLBCL细胞系中，ASPM沉默可抑制细胞生长，诱导细胞凋亡并阻止细胞周期。机械上，ASPM敲低对DLBCL细胞的影响部分取决于其对Wnt /β-catenin途径的阻滞。 结论：总体而言，我们的结果表明ASPM可能作为DLCBL肿瘤发生和预后的预测生物标志物，代表DLCBL的潜在治疗靶标。

关键词: ASPM，弥漫性大B细胞淋巴瘤，生物标志物，预后，细胞生长，肿瘤发生。

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[1]
Campo, E.; Swerdlow, S.H.; Harris, N.L.; Pileri, S.; Stein, H.; Jaffe, E.S. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood, 2011, 117(19), 5019-5032.
[http://dx.doi.org/10.1182/blood-2011-01-293050] [PMID: 21300984]
[2]
van de Schans, S.A.; Wymenga, A.N.; van Spronsen, D.J.; Schouten, H.C.; Coebergh, J.W.; Janssen-Heijnen, M.L. Two sides of the medallion: poor treatment tolerance but better survival by standard chemotherapy in elderly patients with advanced-stage diffuse large B-cell lymphoma. Ann. Oncol., 2012, 23(5), 1280-1286.
[http://dx.doi.org/10.1093/annonc/mdr411] [PMID: 21948810]
[3]
Ripoll, P.; Pimpinelli, S.; Valdivia, M.M.; Avila, J. A cell division mutant of Drosophila with a functionally abnormal spindle. Cell, 1985, 41(3), 907-912.
[http://dx.doi.org/10.1016/S0092-8674(85)80071-4] [PMID: 3924413]
[4]
Kouprina, N.; Pavlicek, A.; Collins, N.K.; Nakano, M.; Noskov, V.N.; Ohzeki, J.; Mochida, G.H.; Risinger, J.I.; Goldsmith, P.; Gunsior, M.; Solomon, G.; Gersch, W.; Kim, J.H.; Barrett, J.C.; Walsh, C.A.; Jurka, J.; Masumoto, H.; Larionov, V. The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein. Hum. Mol. Genet., 2005, 14(15), 2155-2165.
[http://dx.doi.org/10.1093/hmg/ddi220] [PMID: 15972725]
[5]
Paramasivam, M.; Chang, Y.J.; LoTurco, J.J. ASPM and citron kinase co-localize to the midbody ring during cytokinesis. Cell Cycle, 2007, 6(13), 1605-1612.
[http://dx.doi.org/10.4161/cc.6.13.4356] [PMID: 17534152]
[6]
Higgins, J.; Midgley, C.; Bergh, A.M.; Bell, S.M.; Askham, J.M.; Roberts, E.; Binns, R.K.; Sharif, S.M.; Bennett, C.; Glover, D.M.; Woods, C.G.; Morrison, E.E.; Bond, J. Human ASPM participates in spindle organisation, spindle orientation and cytokinesis. BMC Cell Biol., 2010, 11, 85.
[http://dx.doi.org/10.1186/1471-2121-11-85] [PMID: 21044324]
[7]
van der Voet, M.; Berends, C.W.; Perreault, A.; Nguyen-Ngoc, T.; Gönczy, P.; Vidal, M.; Boxem, M.; van den Heuvel, S. NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/GPR/Galpha. Nat. Cell Biol., 2009, 11(3), 269-277.
[http://dx.doi.org/10.1038/ncb1834] [PMID: 19219036]
[8]
Pulvers, J.N.; Bryk, J.; Fish, J.L.; Wilsch-Bräuninger, M.; Arai, Y.; Schreier, D.; Naumann, R.; Helppi, J.; Habermann, B.; Vogt, J.; Nitsch, R.; Tóth, A.; Enard, W.; Pääbo, S.; Huttner, W.B. Mutations in mouse Aspm (abnormal spindle-like microcephaly associated) cause not only microcephaly but also major defects in the germline. Proc. Natl. Acad. Sci. USA, 2010, 107(38), 16595-16600.
[http://dx.doi.org/10.1073/pnas.1010494107] [PMID: 20823249]
[9]
Bond, J.; Scott, S.; Hampshire, D.J.; Springell, K.; Corry, P.; Abramowicz, M.J.; Mochida, G.H.; Hennekam, R.C.; Maher, E.R.; Fryns, J.P.; Alswaid, A.; Jafri, H.; Rashid, Y.; Mubaidin, A.; Walsh, C.A.; Roberts, E.; Woods, C.G. Protein-truncating mutations in ASPM cause variable reduction in brain size. Am. J. Hum. Genet., 2003, 73(5), 1170-1177.
[http://dx.doi.org/10.1086/379085] [PMID: 14574646]
[10]
Kouprina, N.; Pavlicek, A.; Mochida, G.H.; Solomon, G.; Gersch, W.; Yoon, Y.H.; Collura, R.; Ruvolo, M.; Barrett, J.C.; Woods, C.G.; Walsh, C.A.; Jurka, J.; Larionov, V. Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion. PLoS Biol., 2004, 2(5)E126
[http://dx.doi.org/10.1371/journal.pbio.0020126] [PMID: 15045028]
[11]
Johnson, M.B.; Sun, X.; Kodani, A.; Borges-Monroy, R.; Girskis, K.M.; Ryu, S.C.; Wang, P.P.; Patel, K.; Gonzalez, D.M.; Woo, Y.M.; Yan, Z.; Liang, B.; Smith, R.S.; Chatterjee, M.; Coman, D.; Papademetris, X.; Staib, L.H.; Hyder, F.; Mandeville, J.B.; Grant, P.E.; Im, K.; Kwak, H.; Engelhardt, J.F.; Walsh, C.A.; Bae, B.I. Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size. Nature, 2018, 556(7701), 370-375.
[http://dx.doi.org/10.1038/s41586-018-0035-0] [PMID: 29643508]
[12]
Lin, S.Y.; Pan, H.W.; Liu, S.H.; Jeng, Y.M.; Hu, F.C.; Peng, S.Y.; Lai, P.L.; Hsu, H.C. ASPM is a novel marker for vascular invasion, early recurrence, and poor prognosis of hepatocellular carcinoma. Clin. Cancer Res., 2008, 14(15), 4814-4820.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-5262] [PMID: 18676753]
[13]
Bikeye, S.N.; Colin, C.; Marie, Y.; Vampouille, R.; Ravassard, P.; Rousseau, A.; Boisselier, B.; Idbaih, A.; Calvo, C.F.; Leuraud, P.; Lassalle, M.; El Hallani, S.; Delattre, J.Y.; Sanson, M. ASPM-associated stem cell proliferation is involved in malignant progression of gliomas and constitutes an attractive therapeutic target. Cancer Cell Int., 2010, 10, 1.
[http://dx.doi.org/10.1186/1475-2867-10-1] [PMID: 20142996]
[14]
Brüning-Richardson, A.; Bond, J.; Alsiary, R.; Richardson, J.; Cairns, D.A.; McCormack, L.; Hutson, R.; Burns, P.; Wilkinson, N.; Hall, G.D.; Morrison, E.E.; Bell, S.M. ASPM and microcephalin expression in epithelial ovarian cancer correlates with tumour grade and survival. Br. J. Cancer, 2011, 104(10), 1602-1610.
[http://dx.doi.org/10.1038/bjc.2011.117] [PMID: 21505456]
[15]
Pai, V.C.; Hsu, C.C.; Chan, T.S.; Liao, W.Y.; Chuu, C.P.; Chen, W.Y.; Li, C.R.; Lin, C.Y.; Huang, S.P.; Chen, L.T.; Tsai, K.K. ASPM promotes prostate cancer stemness and progression by augmenting Wnt-Dvl-3-β-catenin signaling. Oncogene, 2018.
[PMID: 30266990]
[16]
Xu, Z.; Zhang, Q.; Luh, F.; Jin, B.; Liu, X. Overexpression of the ASPM gene is associated with aggressiveness and poor outcome in bladder cancer. Oncol. Lett., 2019, 17(2), 1865-1876.
[PMID: 30675249]
[17]
Bouska, A.; Bi, C.; Lone, W.; Zhang, W.; Kedwaii, A.; Heavican, T.; Lachel, C.M.; Yu, J.; Ferro, R.; Eldorghamy, N.; Greiner, T.C.; Vose, J.; Weisenburger, D.D.; Gascoyne, R.D.; Rosenwald, A.; Ott, G.; Campo, E.; Rimsza, L.M.; Jaffe, E.S.; Braziel, R.M.; Siebert, R.; Miles, R.R.; Dave, S.; Reddy, A.; Delabie, J.; Staudt, L.M.; Song, J.Y.; McKeithan, T.W.; Fu, K.; Green, M.; Chan, W.C.; Iqbal, J. Adult high-grade B-cell lymphoma with Burkitt lymphoma signature: genomic features and potential therapeutic targets. Blood, 2017, 130(16), 1819-1831.
[http://dx.doi.org/10.1182/blood-2017-02-767335] [PMID: 28801451]
[18]
Schrader, A.; Meyer, K.; Walther, N.; Stolz, A.; Feist, M.; Hand, E.; von Bonin, F.; Evers, M.; Kohler, C.; Shirneshan, K.; Vockerodt, M.; Klapper, W.; Szczepanowski, M.; Murray, P.G.; Bastians, H.; Trümper, L.; Spang, R.; Kube, D. Identification of a new gene regulatory circuit involving B cell receptor activated signaling using a combined analysis of experimental, clinical and global gene expression data. Oncotarget, 2016, 7(30), 47061-47081.
[http://dx.doi.org/10.18632/oncotarget.9219] [PMID: 27166259]
[19]
Rhodes, D.R.; Yu, J.; Shanker, K.; Deshpande, N.; Varambally, R.; Ghosh, D.; Barrette, T.; Pandey, A.; Chinnaiyan, A.M. ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia, 2004, 6(1), 1-6.
[http://dx.doi.org/10.1016/S1476-5586(04)80047-2] [PMID: 15068665]
[20]
Edgar, R.; Domrachev, M.; Lash, A.E. Gene expression omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res., 2002, 30(1), 207-210.
[http://dx.doi.org/10.1093/nar/30.1.207] [PMID: 11752295]
[21]
Gao, J.; Aksoy, B.A.; Dogrusoz, U.; Dresdner, G.; Gross, B.; Sumer, S.O.; Sun, Y.; Jacobsen, A.; Sinha, R.; Larsson, E.; Cerami, E.; Sander, C.; Schultz, N. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal., 2013, 6(269), pl1.
[http://dx.doi.org/10.1126/scisignal.2004088] [PMID: 23550210]
[22]
Kanehisa, M. The KEGG database. Novartis Found Symp, 2002, 247, 91-101. discussion 101-103, 119-128, 244-252.
[http://dx.doi.org/10.1002/0470857897.ch8]
[23]
Huang, D.W.; Sherman, B.T.; Tan, Q.; Collins, J.R.; Alvord, W.G.; Roayaei, J.; Stephens, R.; Baseler, M.W.; Lane, H.C.; Lempicki, R.A. The DAVID gene functional classification tool: a novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol., 2007, 8(9), R183.
[http://dx.doi.org/10.1186/gb-2007-8-9-r183] [PMID: 17784955]
[24]
Cheson, B.D.; Pfistner, B.; Juweid, M.E.; Gascoyne, R.D.; Specht, L.; Horning, S.J.; Coiffier, B.; Fisher, R.I.; Hagenbeek, A.; Zucca, E.; Rosen, S.T.; Stroobants, S.; Lister, T.A.; Hoppe, R.T.; Dreyling, M.; Tobinai, K.; Vose, J.M.; Connors, J.M.; Federico, M.; Diehl, V. International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J. Clin. Oncol., 2007, 25(5), 579-586.
[http://dx.doi.org/10.1200/JCO.2006.09.2403] [PMID: 17242396]
[25]
Chen, X.; Huang, L.; Yang, Y.; Chen, S.; Sun, J.; Ma, C.; Xie, J.; Song, Y.; Yang, J. ASPM promotes glioblastoma growth by regulating G1 restriction point progression and Wnt-β-catenin signaling. Aging (Albany NY), 2020, 12(1), 224-241.
[http://dx.doi.org/10.18632/aging.102612] [PMID: 31905171]
[26]
Hsu, C.C.; Liao, W.Y.; Chan, T.S.; Chen, W.Y.; Lee, C.T.; Shan, Y.S.; Huang, P.J.; Hou, Y.C.; Li, C.R.; Tsai, K.K. The differential distributions of ASPM isoforms and their roles in Wnt signaling, cell cycle progression, and pancreatic cancer prognosis. J. Pathol., 2019, 249(4), 498-508.
[http://dx.doi.org/10.1002/path.5341] [PMID: 31465125]
[27]
Li, S.; Young, K.H.; Medeiros, L.J. Diffuse large B-cell lymphoma. Pathology, 2018, 50(1), 74-87.
[http://dx.doi.org/10.1016/j.pathol.2017.09.006] [PMID: 29167021]
[28]
Xie, J.J.; Zhuo, Y.J.; Zheng, Y.; Mo, R.J.; Liu, Z.Z.; Li, B.W.; Cai, Z.D.; Zhu, X.J.; Liang, Y.X.; He, H.C.; Zhong, W.D. High expression of ASPM correlates with tumor progression and predicts poor outcome in patients with prostate cancer. Int. Urol. Nephrol., 2017, 49(5), 817-823.
[http://dx.doi.org/10.1007/s11255-017-1545-7] [PMID: 28213802]
[29]
Kato, T.A.; Okayasu, R.; Jeggo, P.A.; Fujimori, A. ASPM influences DNA double-strand break repair and represents a potential target for radiotherapy. Int. J. Radiat. Biol., 2011, 87(12), 1189-1195.
[http://dx.doi.org/10.3109/09553002.2011.624152] [PMID: 21923303]
[30]
Woods, D.; Turchi, J.J. Chemotherapy induced DNA damage response: convergence of drugs and pathways. Cancer Biol. Ther., 2013, 14(5), 379-389.
[http://dx.doi.org/10.4161/cbt.23761] [PMID: 23380594]
[31]
Nusse, R.; Clevers, H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell, 2017, 169(6), 985-999.
[http://dx.doi.org/10.1016/j.cell.2017.05.016] [PMID: 28575679]
[32]
Buchman, J.J.; Durak, O.; Tsai, L.H. ASPM regulates Wnt signaling pathway activity in the developing brain. Genes Dev., 2011, 25(18), 1909-1914.
[http://dx.doi.org/10.1101/gad.16830211] [PMID: 21937711]

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