Nucleolin overexpression is associated with an unfavorable outcome for ependymoma: a multifactorial analysis of 176 patients

详细信息    查看全文

• 作者：Chunjui Chen ; Lingchao Chen ; Yu Yao ; Zhiyong Qin ; Hong Chen
• 关键词：Ependymoma ; Nucleolin ; Epidermal growth factor receptor ; Caveolin ; 1
• 刊名：Journal of Neuro-Oncology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：127
• 期：1
• 页码：43-52
• 全文大小：2,020 KB
• 参考文献：1.Godfraind C (2009) Classification and controversies in pathology of ependymomas. Childs Nerv Syst 25:1185–1193CrossRef PubMed
  2.Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Kruchko C, Barnholtz-Sloan J (2014) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007–2011. Neuro Oncol 16(Suppl 4):v1–v63CrossRef
  3.Metellus P, Guyotat J, Chinot O, Durand A, Barrie M, Giorgi R, Jouvet A, Figarella-Branger D (2010) Adult intracranial WHO grade II ependymomas: long-term outcome and prognostic factor analysis in a series of 114 patients. Neuro Oncol 12:976–984PubMedCentral CrossRef PubMed
  4.Reni M, Brandes AA, Vavassori V, Cavallo G, Casagrande F, Vastola F, Magli A, Franzin A, Basso U, Villa E (2004) A multicenter study of the prognosis and treatment of adult brain ependymal tumors. Cancer 100:1221–1229CrossRef PubMed
  5.McLendon RE, Lipp E, Satterfield D, Ehinger M, Austin A, Fleming D, Perkinson K, Lefaivre M, Zagzag D, Wiener B, Gururangan S, Fuchs H, Friedman HS, Herndon JN, Healy P (2015) Prognostic marker analysis in pediatric intracranial ependymomas. J Neurooncol 122(2):255–261CrossRef PubMed
  6.Vera-Bolanos E, Aldape K, Yuan Y, Wu J, Wani K, Necesito-Reyes MJ, Colman H, Dhall G, Lieberman FS, Metellus P, Mikkelsen T, Omuro A, Partap S, Prados M, Robins HI, Soffietti R, Wu J, Gilbert MR, Armstrong TS (2014) Clinical course and progression-free survival of adult intracranial and spinal ependymoma patients. Neuro Oncol 17(3):440–447PubMed
  7.Guyotat J, Signorelli F, Desme S, Frappaz D, Madarassy G, Montange MF, Jouvet A, Bret P (2002) Intracranial ependymomas in adult patients: analyses of prognostic factors. J Neurooncol 60:255–268CrossRef PubMed
  8.Li AM, Dunham C, Tabori U, Carret AS, McNeely PD, Johnston D, Lafay-Cousin L, Wilson B, Eisenstat DD, Jabado N, Zelcer S, Silva M, Scheinemann K, Fryer C, Hendson G, Fotovati A, Hawkins C, Yip S, Dunn SE, Hukin J (2015) EZH2 expression is a prognostic factor in childhood intracranial ependymoma: a canadian pediatric brain tumor consortium study. Cancer 121(9):1499–1507CrossRef PubMed
  9.Mendrzyk F, Korshunov A, Benner A, Toedt G, Pfister S, Radlwimmer B, Lichter P (2006) Identification of gains on 1q and epidermal growth factor receptor overexpression as independent prognostic markers in intracranial ependymoma. Clin Cancer Res 12:2070–2079CrossRef PubMed
  10.Senetta R, Miracco C, Lanzafame S, Chiusa L, Caltabiano R, Galia A, Stella G, Cassoni P (2011) Epidermal growth factor receptor and caveolin-1 coexpression identifies adult supratentorial ependymomas with rapid unfavorable outcomes. Neuro Oncol 13:176–183PubMedCentral CrossRef PubMed
  11.Modena P, Buttarelli FR, Miceli R, Piccinin E, Baldi C, Antonelli M, Morra I, Lauriola L, Di Rocco C, Garre ML, Sardi I, Genitori L, Maestro R, Gandola L, Facchinetti F, Collini P, Sozzi G, Giangaspero F, Massimino M (2012) Predictors of outcome in an AIEOP series of childhood ependymomas: a multifactorial analysis. Neuro Oncol 14:1346–1356PubMedCentral CrossRef PubMed
  12.Ridley L, Rahman R, Brundler MA, Ellison D, Lowe J, Robson K, Prebble E, Luckett I, Gilbertson RJ, Parkes S, Rand V, Coyle B, Grundy RG (2008) Multifactorial analysis of predictors of outcome in pediatric intracranial ependymoma. Neuro Oncol 10:675–689PubMedCentral CrossRef PubMed
  13.Xu Z, Joshi N, Agarwal A, Dahiya S, Bittner P, Smith E, Taylor S, Piwnica-Worms D, Weber J, Leonard JR (2012) Knocking down nucleolin expression in gliomas inhibits tumor growth and induces cell cycle arrest. J Neurooncol 108:59–67CrossRef PubMed
  14.Yang X, Xu Z, Li D, Cheng S, Fan K, Li C, Li A, Zhang J, Feng M (2013) Cell surface nucleolin is crucial in the activation of the CXCL12/CXCR4 signaling pathway. Tumour Biol 35(1):333–338CrossRef PubMed
  15.Shen N, Yan F, Pang J, Wu LC, Al-Kali A, Litzow MR, Liu S (2014) A nucleolin-DNMT1 regulatory axis in acute myeloid leukemogenesis. Oncotarget 5:5494–5509PubMedCentral CrossRef PubMed
  16.Orrick LR, Olson MO, Busch H (1973) Comparison of nucleolar proteins of normal rat liver and Novikoff hepatoma ascites cells by two-dimensional polyacrylamide gel electrophoresis. Proc Natl Acad Sci USA 70:1316–1320PubMedCentral CrossRef PubMed
  17.Khurts S, Masutomi K, Delgermaa L, Arai K, Oishi N, Mizuno H, Hayashi N, Hahn WC, Murakami S (2004) Nucleolin interacts with telomerase. J Biol Chem 279:51508–51515CrossRef PubMed
  18.Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O’Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110PubMedCentral CrossRef PubMed
  19.Cassoni P, Senetta R, Castellano I, Ortolan E, Bosco M, Magnani I, Ducati A (2007) Caveolin-1 expression is variably displayed in astroglial-derived tumors and absent in oligodendrogliomas: concrete premises for a new reliable diagnostic marker in gliomas. Am J Surg Pathol 31:760–769CrossRef PubMed
  20.Bender FC, Reymond MA, Bron C, Quest AF (2000) Caveolin-1 levels are down-regulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity. Cancer Res 60:5870–5878PubMed
  21.Kato K, Hida Y, Miyamoto M, Hashida H, Shinohara T, Itoh T, Okushiba S, Kondo S, Katoh H (2002) Overexpression of caveolin-1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage. Cancer 94:929–933CrossRef PubMed
  22.Kannan A, Krishnan A, Ali M, Subramaniam S, Halagowder D, Sivasithamparam ND (2014) Caveolin-1 promotes gastric cancer progression by up-regulating epithelial to mesenchymal transition by crosstalk of signalling mechanisms under hypoxic condition. Eur J Cancer 50:204–215CrossRef PubMed
  23.Abulrob A, Giuseppin S, Andrade MF, McDermid A, Moreno M, Stanimirovic D (2004) Interactions of EGFR and caveolin-1 in human glioblastoma cells: evidence that tyrosine phosphorylation regulates EGFR association with caveolae. Oncogene 23:6967–6979CrossRef PubMed
  24.Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, Zheng S, Chakravarty D, Sanborn JZ, Berman SH, Beroukhim R, Bernard B, Wu CJ, Genovese G, Shmulevich I, Barnholtz-Sloan J, Zou L, Vegesna R, Shukla SA, Ciriello G, Yung WK, Zhang W, Sougnez C, Mikkelsen T, Aldape K, Bigner DD, Van Meir EG, Prados M, Sloan A, Black KL, Eschbacher J, Finocchiaro G, Friedman W, Andrews DW, Guha A, Iacocca M, O’Neill BP, Foltz G, Myers J, Weisenberger DJ, Penny R, Kucherlapati R, Perou CM, Hayes DN, Gibbs R, Marra M, Mills GB, Lander E, Spellman P, Wilson R, Sander C, Weinstein J, Meyerson M, Gabriel S, Laird PW, Haussler D, Getz G, Chin L (2013) The somatic genomic landscape of glioblastoma. Cell 155:462–477PubMedCentral CrossRef PubMed
  25.Furnari FB, Cloughesy TF, Cavenee WK, Mischel PS (2015) Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma. Nat Rev Cancer 15:302–310CrossRef PubMed
  26.Pajtler KW, Witt H, Sill M, Jones DT, Hovestadt V, Kratochwil F, Wani K, Tatevossian R, Punchihewa C, Johann P, Reimand J, Warnatz HJ, Ryzhova M, Mack S, Ramaswamy V, Capper D, Schweizer L, Sieber L, Wittmann A, Huang Z, van Sluis P, Volckmann R, Koster J, Versteeg R, Fults D, Toledano H, Avigad S, Hoffman LM, Donson AM, Foreman N, Hewer E, Zitterbart K, Gilbert M, Armstrong TS, Gupta N, Allen JC, Karajannis MA, Zagzag D, Hasselblatt M, Kulozik AE, Witt O, Collins VP, von Hoff K, Rutkowski S, Pietsch T, Bader G, Yaspo ML, von Deimling A, Lichter P, Taylor MD, Gilbertson R, Ellison DW, Aldape K, Korshunov A, Kool M, Pfister SM (2015) Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell 27:728–743PubMedCentral CrossRef PubMed
  27.Archer TC, Pomeroy SL (2015) Defining the molecular landscape of ependymomas. Cancer Cell 27:613–615CrossRef PubMed
  28.Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S, Stutz AM, Wang X, Gallo M, Garzia L, Zayne K, Zhang X, Ramaswamy V, Jager N, Jones DT, Sill M, Pugh TJ, Ryzhova M, Wani KM, Shih DJ, Head R, Remke M, Bailey SD, Zichner T, Faria CC, Barszczyk M, Stark S, Seker-Cin H, Hutter S, Johann P, Bender S, Hovestadt V, Tzaridis T, Dubuc AM, Northcott PA, Peacock J, Bertrand KC, Agnihotri S, Cavalli FM, Clarke I, Nethery-Brokx K, Creasy CL, Verma SK, Koster J, Wu X, Yao Y, Milde T, Sin-Chan P, Zuccaro J, Lau L, Pereira S, Castelo-Branco P, Hirst M, Marra MA, Roberts SS, Fults D, Massimi L, Cho YJ, Van Meter T, Grajkowska W, Lach B, Kulozik AE, von Deimling A, Witt O, Scherer SW, Fan X, Muraszko KM, Kool M, Pomeroy SL, Gupta N, Phillips J, Huang A, Tabori U, Hawkins C, Malkin D, Kongkham PN, Weiss WA, Jabado N, Rutka JT, Bouffet E, Korbel JO, Lupien M, Aldape KD, Bader GD, Eils R, Lichter P, Dirks PB, Pfister SM, Korshunov A, Taylor MD (2014) Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature 506:445–450PubMedCentral CrossRef PubMed
  29.Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs K, Yergeau D, Vadodaria B, Mulder HL, Becksford J, Gupta P, Huether R, Ma J, Song G, Gajjar A, Merchant T, Boop F, Smith AA, Ding L, Lu C, Ochoa K, Zhao D, Fulton RS, Fulton LL, Mardis ER, Wilson RK, Downing JR, Green DR, Zhang J, Ellison DW, Gilbertson RJ (2014) C11orf95-RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature 506:451–455PubMedCentral CrossRef PubMed
  30.Armstrong TS, Vera-Bolanos E, Bekele BN, Aldape K, Gilbert MR (2010) Adult ependymal tumors: prognosis and the M. D. Anderson Cancer Center experience. Neuro Oncol 12:862–870PubMedCentral CrossRef PubMed
  31.Gatta G, Botta L, Rossi S, Aareleid T, Bielska-Lasota M, Clavel J, Dimitrova N, Jakab Z, Kaatsch P, Lacour B, Mallone S, Marcos-Gragera R, Minicozzi P, Sanchez-Perez MJ, Sant M, Santaquilani M, Stiller C, Tavilla A, Trama A, Visser O, Peris-Bonet R (2014) Childhood cancer survival in Europe 1999-2007: results of EUROCARE-5–a population-based study. Lancet Oncol 15:35–47CrossRef PubMed
  32.Archer TC, Pomeroy SL (2011) Posterior fossa ependymomas: a tale of two subtypes. Cancer Cell 20:133–134CrossRef PubMed
  33.Merchant TE, Li C, Xiong X, Kun LE, Boop FA, Sanford RA (2009) Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol 10:258–266PubMedCentral CrossRef PubMed
  34.Kilday JP, Rahman R, Dyer S, Ridley L, Lowe J, Coyle B, Grundy R (2009) Pediatric ependymoma: biological perspectives. Mol Cancer Res 7:765–786CrossRef PubMed
  35.Strother DR, Lafay-Cousin L, Boyett JM, Burger P, Aronin P, Constine L, Duffner P, Kocak M, Kun LE, Horowitz ME, Gajjar A (2013) Benefit from prolonged dose-intensive chemotherapy for infants with malignant brain tumors is restricted to patients with ependymoma: a report of the Pediatric Oncology Group randomized controlled trial 9233/34. Neuro Oncol
  
• 作者单位：Chunjui Chen (1)
  Lingchao Chen (1)
  Yu Yao (1)
  Zhiyong Qin (1)
  Hong Chen (2)
  
  1. Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, No 12, Middle Wulumuqi Road, Shanghai, 200040, China
  2. Department of Neuropathology, Huashan Hospital Shanghai Medical College, Fudan University, No 12, Middle Wulumuqi Road, Shanghai, 200040, China
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7373

文摘

Ependymoma typically has a better overall survival rate than most gliomas. Only a few comprehensive clinical studies have been published, but these are mostly from Western countries and use small sample sizes. Histopathological classification is not sufficient to show variable outcomes, and fails to show prognostic markers of the diverse outcomes; hence, it is essential to understand biological mechanisms. In this study, 176 ependymoma samples (World Health Organization grade II and III) were reviewed at Huashan Hospital. Both children and adults were included. We performed multifactorial analyses of clinical prognostic factors and the biomolecular marker expressions of nucleolin, epidermal growth factor receptor (EGFR) and caveolae-associated protein caveolin-1 by immunohistochemistry. We identified the probabilities of progression-free survival and overall survival using univariate and multivariate statistical methods. The participants were diagnosed with ependymomas between 2002 and 2010, including distributions of tumor locations in intracranial and extracranial regions. Nucleolin was overexpressed in 67 % of our samples, demonstrating a subgroup with poor outcome; particularly infratentorial and anaplastic ependymomas. There was no significant correlation between the expression of EGFR and caveolin-1 and clinical outcomes. Clinically, inferior prognosis was observed with regard to age (<18 years), intracranial location, high grade ependymomas, and incomplete resection. We found that nucleolin was an unfavorable prognostic predictor for ependymomas. Moreover, our findings show a subset of aggravating outcomes in high-grade and posterior fossa tumors.