Genetic Prognostic Factors in Adult Diffuse Gliomas: A 10-Year Experience at a Single Institution

Author:

Barzegar Behrooz Amir123ORCID,Darzi Ramandi Hadi456,Latifi-Navid Hamid278,Peymani Payam9ORCID,Tarharoudi Rahil310,Momeni Nasrin310,Sabaghpour Azarian Mohammad Mehdi11ORCID,Eltonsy Sherif9ORCID,Pour-Rashidi Ahmad312ORCID,Ghavami Saeid11314ORCID

Affiliation:

1. Department of Human Anatomy and Cell Science, University of Manitoba College of Medicine, Winnipeg, MB R3E 0J9, Canada

2. Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran 1416634793, Iran

3. Brain Cancer Research Group, Department of Cancer, Asu Vanda Gene Industrial Research Company, Tehran 1533666398, Iran

4. Department of Plant Production and Genetics, Bu-Ali Sina University, Hamedan 6517838623, Iran

5. Department of Molecular Physiology, Agricultural Biotechnology Research Institute of Iran, Agricultural Research Education and Extension Organization (AREEO), Karaj 7155863511, Iran

6. Department of Biostatistics, Asu Vanda Gene Industrial Research Company, Tehran 1533666398, Iran

7. Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, P.O. Box 14965/161, Tehran 1497716316, Iran

8. School of Biological Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran 1953833511, Iran

9. College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada

10. Department of Molecular and Cellular Sciences, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran 1477893855, Iran

11. Department of Biotechnology, Asu Vanda Gene Industrial Research Company, Tehran 1533666398, Iran

12. Department of Neurosurgery, Sina Hospital, Tehran University of Medical Sciences, Tehran 1416634793, Iran

13. Research Institute of Oncology and Hematology, Cancer Care Manitoba-University of Manitoba, Winnipeg, MB R3E 0V9, Canada

14. Biology of Breathing Theme, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3T 2N2, Canada

Abstract

Gliomas are primary brain lesions involving cerebral structures without well-defined boundaries and constitute the most prevalent central nervous system (CNS) neoplasms. Among gliomas, glioblastoma (GB) is a glioma of the highest grade and is associated with a grim prognosis. We examined how clinical variables and molecular profiles may have affected overall survival (OS) over the past ten years. A retrospective study was conducted at Sina Hospital in Tehran, Iran and examined patients with confirmed glioma diagnoses between 2012 and 2020. We evaluated the correlation between OS in GB patients and sociodemographic as well as clinical factors and molecular profiling based on IDH1, O-6-Methylguanine-DNA Methyltransferase (MGMT), TERTp, and epidermal growth factor receptor (EGFR) amplification (EGFR-amp) status. Kaplan–Meier and multivariate Cox regression models were used to assess patient survival. A total of 178 patients were enrolled in the study. The median OS was 20 months, with a 2-year survival rate of 61.0%. Among the 127 patients with available IDH measurements, 100 (78.7%) exhibited mutated IDH1 (IDH1-mut) tumors. Of the 127 patients with assessed MGMT promoter methylation (MGMTp-met), 89 (70.1%) had MGMT methylated tumors. Mutant TERTp (TERTp-mut) was detected in 20 out of 127 cases (15.7%), while wildtype TERTp (wildtype TERTp-wt) was observed in 107 cases (84.3%). Analyses using multivariable models revealed that age at histological grade (p < 0.0001), adjuvant radiotherapy (p < 0.018), IDH1 status (p < 0.043), and TERT-p status (p < 0.014) were independently associated with OS. Our study demonstrates that patients with higher tumor histological grades who had received adjuvant radiotherapy exhibited IDH1-mut or presented with TERTp-wt experienced improved OS. Besides, an interesting finding showed an association between methylation of MGMTp and TERTp status with tumor location.

Publisher

MDPI AG

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