GABAergic system gene expression predicts clinical outcome in patients with neuroblastoma

Stephen S. Roberts, Motomi (Tomi) Mori, Patrick Pattee, Jodi Lapidas, Ravi Matthews, Jean P. O'Malley, Yi Ching Hsieh, Mark A. Turner, Zhaohong Wang, Qi Tian, Matthew J. Rodland, C. Patrick Reynolds, Robert C. Seeger, Srinivasa R. Nagalla

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Purpose: Neuroblastoma (NB) is a common childhood malignancy characterized by heterogeneous clinical behavior. The purpose of this study was to identify potential NB biomarkers that may improve outcome prediction. Patients and Methods: The suppression subtractive hybridization (SSH) technique was used to identify the genes differentially expressed between NB and control tissue. RNA isolated from 235 primary NB tumor samples obtained from the Children's Cancer Group was evaluated for expression of the candidate markers using quantitative reverse transcriptase polymerase chain reaction (Taqman assays). The association between the mRNA expression levels in the identified candidate genes and clinical outcome was evaluated. Results: SSH analysis identified differential expression of members of the GABAergic gene family in NB. Lower levels of gamma-aminobutyric acid (GABA) receptor-associated protein (GABARAP) gene expression predict decreased survival among all patients. GABAA δ receptor subunit gene expression was predictive of a poor outcome among Evans stage IV-S patients. An index of five coexpressed GABAA receptor subunits was identified (GABAA profile [GAP score]). Patients with a higher GAP score (> -1) had a survival advantage. Multivariate analysis showed that GABARAP and GABAA a2 receptor subunit gene expression levels and GAP score remained predictors of clinical outcome after accounting for current prognostic indicators. Conclusion: Dysregulation of the GABAergic system may constitute a fundamental event in the development of NB, and assessment of GABAergic system gene expression could provide improved patient stratification and potential new therapies.

Original languageEnglish (US)
Pages (from-to)4127-4134
Number of pages8
JournalJournal of Clinical Oncology
Volume22
Issue number20
DOIs
StatePublished - 2004

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Neuroblastoma
Gene Expression
GABA-A Receptors
GABA Receptors
Genes
Neoplasms
Survival
Reverse Transcriptase Polymerase Chain Reaction
Proteins
Multivariate Analysis
Biomarkers
RNA
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Roberts, S. S., Mori, M. T., Pattee, P., Lapidas, J., Matthews, R., O'Malley, J. P., ... Nagalla, S. R. (2004). GABAergic system gene expression predicts clinical outcome in patients with neuroblastoma. Journal of Clinical Oncology, 22(20), 4127-4134. https://doi.org/10.1200/JCO.2004.02.032

GABAergic system gene expression predicts clinical outcome in patients with neuroblastoma. / Roberts, Stephen S.; Mori, Motomi (Tomi); Pattee, Patrick; Lapidas, Jodi; Matthews, Ravi; O'Malley, Jean P.; Hsieh, Yi Ching; Turner, Mark A.; Wang, Zhaohong; Tian, Qi; Rodland, Matthew J.; Reynolds, C. Patrick; Seeger, Robert C.; Nagalla, Srinivasa R.

In: Journal of Clinical Oncology, Vol. 22, No. 20, 2004, p. 4127-4134.

Research output: Contribution to journalArticle

Roberts, SS, Mori, MT, Pattee, P, Lapidas, J, Matthews, R, O'Malley, JP, Hsieh, YC, Turner, MA, Wang, Z, Tian, Q, Rodland, MJ, Reynolds, CP, Seeger, RC & Nagalla, SR 2004, 'GABAergic system gene expression predicts clinical outcome in patients with neuroblastoma', Journal of Clinical Oncology, vol. 22, no. 20, pp. 4127-4134. https://doi.org/10.1200/JCO.2004.02.032
Roberts, Stephen S. ; Mori, Motomi (Tomi) ; Pattee, Patrick ; Lapidas, Jodi ; Matthews, Ravi ; O'Malley, Jean P. ; Hsieh, Yi Ching ; Turner, Mark A. ; Wang, Zhaohong ; Tian, Qi ; Rodland, Matthew J. ; Reynolds, C. Patrick ; Seeger, Robert C. ; Nagalla, Srinivasa R. / GABAergic system gene expression predicts clinical outcome in patients with neuroblastoma. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 20. pp. 4127-4134.
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abstract = "Purpose: Neuroblastoma (NB) is a common childhood malignancy characterized by heterogeneous clinical behavior. The purpose of this study was to identify potential NB biomarkers that may improve outcome prediction. Patients and Methods: The suppression subtractive hybridization (SSH) technique was used to identify the genes differentially expressed between NB and control tissue. RNA isolated from 235 primary NB tumor samples obtained from the Children's Cancer Group was evaluated for expression of the candidate markers using quantitative reverse transcriptase polymerase chain reaction (Taqman assays). The association between the mRNA expression levels in the identified candidate genes and clinical outcome was evaluated. Results: SSH analysis identified differential expression of members of the GABAergic gene family in NB. Lower levels of gamma-aminobutyric acid (GABA) receptor-associated protein (GABARAP) gene expression predict decreased survival among all patients. GABAA δ receptor subunit gene expression was predictive of a poor outcome among Evans stage IV-S patients. An index of five coexpressed GABAA receptor subunits was identified (GABAA profile [GAP score]). Patients with a higher GAP score (> -1) had a survival advantage. Multivariate analysis showed that GABARAP and GABAA a2 receptor subunit gene expression levels and GAP score remained predictors of clinical outcome after accounting for current prognostic indicators. Conclusion: Dysregulation of the GABAergic system may constitute a fundamental event in the development of NB, and assessment of GABAergic system gene expression could provide improved patient stratification and potential new therapies.",
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T1 - GABAergic system gene expression predicts clinical outcome in patients with neuroblastoma

AU - Roberts, Stephen S.

AU - Mori, Motomi (Tomi)

AU - Pattee, Patrick

AU - Lapidas, Jodi

AU - Matthews, Ravi

AU - O'Malley, Jean P.

AU - Hsieh, Yi Ching

AU - Turner, Mark A.

AU - Wang, Zhaohong

AU - Tian, Qi

AU - Rodland, Matthew J.

AU - Reynolds, C. Patrick

AU - Seeger, Robert C.

AU - Nagalla, Srinivasa R.

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N2 - Purpose: Neuroblastoma (NB) is a common childhood malignancy characterized by heterogeneous clinical behavior. The purpose of this study was to identify potential NB biomarkers that may improve outcome prediction. Patients and Methods: The suppression subtractive hybridization (SSH) technique was used to identify the genes differentially expressed between NB and control tissue. RNA isolated from 235 primary NB tumor samples obtained from the Children's Cancer Group was evaluated for expression of the candidate markers using quantitative reverse transcriptase polymerase chain reaction (Taqman assays). The association between the mRNA expression levels in the identified candidate genes and clinical outcome was evaluated. Results: SSH analysis identified differential expression of members of the GABAergic gene family in NB. Lower levels of gamma-aminobutyric acid (GABA) receptor-associated protein (GABARAP) gene expression predict decreased survival among all patients. GABAA δ receptor subunit gene expression was predictive of a poor outcome among Evans stage IV-S patients. An index of five coexpressed GABAA receptor subunits was identified (GABAA profile [GAP score]). Patients with a higher GAP score (> -1) had a survival advantage. Multivariate analysis showed that GABARAP and GABAA a2 receptor subunit gene expression levels and GAP score remained predictors of clinical outcome after accounting for current prognostic indicators. Conclusion: Dysregulation of the GABAergic system may constitute a fundamental event in the development of NB, and assessment of GABAergic system gene expression could provide improved patient stratification and potential new therapies.

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