1. Academic Validation
  2. Enrichment of Aldolase C Correlates with Low Non-Mutated IDH1 Expression and Predicts a Favorable Prognosis in Glioblastomas

Enrichment of Aldolase C Correlates with Low Non-Mutated IDH1 Expression and Predicts a Favorable Prognosis in Glioblastomas

  • Cancers (Basel). 2019 Aug 23;11(9):1238. doi: 10.3390/cancers11091238.
Yu-Chan Chang 1 Hsing-Fang Tsai 1 2 Shang-Pen Huang 1 3 Chi-Long Chen 4 5 Michael Hsiao 6 7 Wen-Chiuan Tsai 8
Affiliations

Affiliations

  • 1 Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
  • 2 Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
  • 3 Department of Neurology, Po-Jen General Hospital, Taipei 105, Taiwan.
  • 4 Department of Pathology, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan.
  • 5 Department of Pathology, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
  • 6 Genomics Research Center, Academia Sinica, Taipei 115, Taiwan. mhsiao@gate.sinica.edu.tw.
  • 7 Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. mhsiao@gate.sinica.edu.tw.
  • 8 Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan. ab95057@hotmail.com.
Abstract

The aldolases family is one of the main Enzymes involved in the process of glycolysis. Aldolase C (ALDOC), which belongs to the aldolase family, is found in normal brain tissue and is responsible for the repair of injured tissue. However, the role of ALDOC in glioblastoma remains unclear. In this study, we data-mined in silico databases to evaluate aldolase family members' mRNA expression in glioblastoma patient cohorts for determining its prognostic values. After that, we also performed immunohistochemical stain (IHC) analysis to evaluate protein expression levels of ALDOC in glioblastoma tissues. From The Cancer Genome Atlas (TCGA) database analyses, higher mRNA expression levels in normal brain tissue compared to glioblastoma was observed. In addition, compared to low-grade glioma, ALDOC expression was significantly downregulated in high-grade glioblastoma. Besides, the expression level of ALDOC was associated with molecular subtypes of glioblastomas and recurrent status in several data sets. In contrast, aldolase A (ALDOA) and aldolase B (ALDOB) revealed no significant prognostic impacts in the glioblastoma cohorts. Furthermore, we also proved that ALDOC mRNA and protein expression inversely correlated with non-mutated IDH1 expressions in glioblastoma patient cohorts. Additionally, the concordance of low ALDOC and high non-mutated IDH1 expressions predicted a stronger poor prognosis in glioblastoma patients compared to each of above tests presented alone. The plausible ALDOC and IDH1 regulatory mechanism was further elucidated. Our results support high ALDOC expression in glioblastomas that might imply the mutated status of IDH1, less possibility of mesenchymal subtype, and predict a favorable prognosis.

Keywords

IDH1; aldolase C; glioblastoma; prognostic.

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