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Expression analysis of stem cell-related genes reveal OCT4 as a predictor of poor clinical outcome in medulloblastoma

  • Laboratory Investigation - Human/Animal Tissue
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Abstract

Aberrant expression of stem cell-related genes in tumors may confer more primitive and aggressive traits affecting clinical outcome. Here, we investigated expression and prognostic value of the neural stem cell marker CD133, as well as of the pluripotency genes LIN28 and OCT4 in 37 samples of pediatric medulloblastoma, the most common and challenging type of embryonal tumor. While most medulloblastoma samples expressed CD133 and LIN28, OCT4 expression was found to be more sporadic, with detectable levels occurring in 48% of tumors. Expression levels of OCT4, but not CD133 or LIN28, were significantly correlated with shorter survival (P ≤ 0.0001). Median survival time of patients with tumors hyperexpressing OCT4 and tumors displaying low/undetectable OCT4 expression were 6 and 153 months, respectively. More importantly, when patients were clinically stratified according to their risk of tumor recurrence, positive OCT4 expression in primary tumor specimens could discriminate patients classified as average risk but which further deceased within 5 years of diagnosis (median survival time of 28 months), a poor clinical outcome typical of high risk patients. Our findings reveal a previously unknown prognostic value for OCT4 expression status in medulloblastoma, which might be used as a further indicator of poor survival and aid postoperative treatment selection, with a particular potential benefit for clinically average risk patients.

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References

  1. Guessous F, Li Y, Abounader R (2008) Signaling pathways in medulloblastoma. J Cell Physiol 217:577–583

    Article  PubMed  CAS  Google Scholar 

  2. Kouprina N, Pavlicek A, Collins NK et al (2005) The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein. Hum Mol Genet 14:2155–2165

    Article  PubMed  CAS  Google Scholar 

  3. Mueller S, Chang S (2009) Pediatric brain tumors: current treatment strategies and future therapeutic approaches. Neurotherapeutics 6:570–586

    Article  PubMed  CAS  Google Scholar 

  4. Carlotti CG Jr, Smith C, Rutka JT (2008) The molecular genetics of medulloblastoma: an assessment of new therapeutic targets. Neurosurg Rev 31:359–369

    Article  PubMed  Google Scholar 

  5. Singh SK, Clarke ID, Terasaki M et al (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828

    PubMed  CAS  Google Scholar 

  6. Okamoto OK (2009) Cancer stem cell genomics: the quest for early markers of malignant progression. Expert Rev Mol Diagn 9:545–554

    Article  PubMed  CAS  Google Scholar 

  7. Cheng L, Sung MT, Cossu-Rocca P et al (2007) OCT4: biological functions and clinical applications as a marker of germ cell neoplasia. J Pathol 211:1–9

    Article  PubMed  CAS  Google Scholar 

  8. Gidekel S, Pizov G, Bergman Y, Pikarsky E (2003) Oct-3/4 is a dosedependent oncogenic fate determinant. Cancer Cell 4:361–370

    Article  PubMed  CAS  Google Scholar 

  9. Chang CH, Housepian EM, Herbert C (1969) An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastoma. Radiology 93:1351–1359

    PubMed  CAS  Google Scholar 

  10. Valente V, Teixeira SA, Neder L et al (2009) Selection of suitable housekeeping genes for expression analysis in glioblastoma using quantitative RT-PCR. BMC Mol Biol 3:10–17

    Google Scholar 

  11. Blazek ER, Foutch JL, Maki G (2007) Daoy medulloblastoma cells that express CD133 are radioresistant relative to CD133- cells, and the CD133+ sector is enlarged by hypoxia. Int J Radiat Oncol Biol Phys 67:1–5

    Article  PubMed  CAS  Google Scholar 

  12. Beier D, Wischhusen J, Dietmaier W et al (2008) CD133 expression and cancer stem cells predict prognosis in high-grade oligodendroglial tumors. Brain Pathol 18:370–377

    Article  PubMed  Google Scholar 

  13. Zhang M, Song T, Yang L et al (2008) Nestin and CD133: valuable stem cell-specific markers for determining clinical outcome of glioma patients. J Exp Clin Cancer Res 24:27–85

    Google Scholar 

  14. Richard M, Tan SP, Tan JH et al (2004) The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells 22:51–64

    Article  Google Scholar 

  15. Darr H, Benvenisty N (2009) Genetic analysis of the role of the reprogramming gene LIN-28 in human embryonic stem cells. Stem Cells 27:352–362

    Article  PubMed  CAS  Google Scholar 

  16. Marie SK, Okamoto OK, Uno M et al (2008) Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas. Int J Cancer 122:807–815

    Article  PubMed  CAS  Google Scholar 

  17. Viswanathan SR, Powers JT, Einhorn W et al (2009) Lin28 promotes transformation and is associated with advanced human malignancies. Nat Genet 41:843–848

    Article  PubMed  CAS  Google Scholar 

  18. Lu L, Katsaros D, Shaverdashvili K et al (2009) Pluripotent factor lin-28 and its homologue lin-28b in epithelial ovarian cancer and their associations with disease outcomes and expression of let-7a and IGF-II. Eur J Cancer 45:2212–2218

    Article  PubMed  CAS  Google Scholar 

  19. Dangi-Garimella S, Yun J, Eves EM et al (2009) Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7. EMBO J 28:347–358

    Article  PubMed  CAS  Google Scholar 

  20. Ben-Porath I, Thomson MW, Carey VJ et al (2008) An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40:499–507

    Article  PubMed  CAS  Google Scholar 

  21. Chiou SH, Wang ML, Chou YT et al (2010) Co-expression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res 70:10433–10444

    Article  PubMed  CAS  Google Scholar 

  22. Ge N, Lin HX, Xiao XS et al (2010) Prognostic significance of Oct4 and Sox2 expression in hypopharyngeal squamous cell carcinoma. J Transl Med 8:94

    Article  PubMed  Google Scholar 

  23. Qiu C, Ma Y, Wang J et al (2010) Lin28-mediated post-transcriptional regulation of Oct4 expression in human embryonic stem cells. Nucleic Acids Res 38:1240–1248

    Article  PubMed  CAS  Google Scholar 

  24. Lee SH, Jeyapalan JN, Appleby V et al (2010) Dynamic methylation and expression of Oct4 in early neural stem cells. J Anat 217:203–213

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from INCT-Células Tronco em Doenças Genéticas Humanas, FAPESP, CNPq, and CAPES. C.O.R. and D.E.S. were recipients of fellowships from CAPES and CNPq.

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Authors and Affiliations

  1. Department of Neurology and Neurosurgery, Federal University of São Paulo, São Paulo, SP, Brazil

    Carolina Oliveira Rodini, Daniela Emi Suzuki & Sérgio Cavalheiro

  2. Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, Rua do Matão 277 Cidade Universitária, São Paulo, SP, 05508-090, Brazil

    Carolina Oliveira Rodini, Daniela Emi Suzuki & Oswaldo Keith Okamoto

  3. Institute of Pediatric Oncology (GRAACC), Pediatric Department, Federal University of São Paulo, São Paulo, SP, Brazil

    Najsla Saba-Silva, Andréa Cappellano & Silvia Regina Caminada Toledo

  4. Ludwig Institute for Cancer Research, São Paulo Branch at Hospital Alemão Oswaldo Cruz, São Paulo, SP, Brazil

    Jorge Estefano Santana de Souza

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  1. Carolina Oliveira Rodini
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  2. Daniela Emi Suzuki
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  3. Najsla Saba-Silva
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  5. Jorge Estefano Santana de Souza
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  6. Sérgio Cavalheiro
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  7. Silvia Regina Caminada Toledo
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  8. Oswaldo Keith Okamoto
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Corresponding author

Correspondence to Oswaldo Keith Okamoto.

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Rodini, C.O., Suzuki, D.E., Saba-Silva, N. et al. Expression analysis of stem cell-related genes reveal OCT4 as a predictor of poor clinical outcome in medulloblastoma. J Neurooncol 106, 71–79 (2012). https://doi.org/10.1007/s11060-011-0647-9

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  • DOI: https://doi.org/10.1007/s11060-011-0647-9

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