Tumor Biology

, Volume 37, Issue 5, pp 6935–6942 | Cite as

Aberrant expression of Notch1, HES1, and DTX1 genes in glioblastoma formalin-fixed paraffin-embedded tissues

  • Rajeswari Narayanappa
  • Pritilata Rout
  • Madhuri G. S. Aithal
  • Ashis Kumar Chand
Original Article

Abstract

Glioblastoma is the most common malignant brain tumor accounting for more than 54 % of all gliomas. Despite aggressive treatments, median survival remains less than 1 year. This might be due to the unavailability of effective molecular diagnostic markers and targeted therapy. Thus, it is essential to discover molecular mechanisms underlying disease by identifying dysregulated pathways involved in tumorigenesis. Notch signaling is one such pathway which plays an important role in determining cell fates. Since it is found to play a critical role in many cancers, we investigated the role of Notch genes in glioblastoma with an aim to identify biomarkers that can improve diagnosis. Using real-time PCR, we assessed the expression of Notch genes including receptors (Notch1, Notch2, Notch3, and Notch4), ligands (JAG1, JAG2, and DLL3), downstream targets (HES1 and HEY2), regulator Deltex1 (DTX1), inhibitor NUMB along with transcriptional co-activator MAML1, and a component of gamma-secretase complex APH1A in 15 formalin-fixed paraffin-embedded (FFPE) patient samples. Relative quantification was done by the 2−ΔΔCt method; the data are presented as fold change in gene expression normalized to an internal control gene and relative to the calibrator. The data revealed aberrant expression of Notch genes in glioblastoma compared to normal brain. More than 85 % of samples showed high Notch1 (P = 0.0397) gene expression and low HES1 (P = 0.011) and DTX1 (P = 0.0001) gene expression. Our results clearly show aberrant expression of Notch genes in glioblastoma which can be used as putative biomarkers together with histopathological observation to improve diagnosis, therapeutic strategies, and patient prognosis.

Keywords

Gene expression Notch genes Glioblastoma Biomarker Real-time PCR 

Notes

Acknowledgments

This study was funded by the Department of Science and Technology, New Delhi, India (grant number SR/FT/LS-170/2008). We thank the Brain Bank, NIMHANS, Bangalore, India, for providing the clinical samples.

Compliance with ethical standards

Conflicts of interest

None

Ethical approval

For this type of study, formal consent is not required.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Rajeswari Narayanappa
    • 1
    • 2
  • Pritilata Rout
    • 3
  • Madhuri G. S. Aithal
    • 1
  • Ashis Kumar Chand
    • 4
  1. 1.Department of BiotechnologyDayananda Sagar College of EngineeringBangaloreIndia
  2. 2.Division of Molecular MedicineSt. John’s Research InstituteBangaloreIndia
  3. 3.Department of PathologySt. John’s Medical CollegeBangaloreIndia
  4. 4.Department of NeurosurgerySt. John’s Medical CollegeBangaloreIndia

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