Wajiha Amin1#, Sufiyan Sufiyan1#, Sahar Ilyas2, Altaf Ali Laghari1, Sana Naeem2, Siraj Uddin1, Hamza Bajwa1, Nouman Mughal2,3, Syed Ather Enam1,2
1Department of Surgery, Aga Khan University Hospital, Karachi, Pakistan;
2Centre of Oncological Research in Surgery, Aga Khan University Hospital, Karachi, Pakistan;
3Department of Biological and Biomedical Sciences, Aga Khan University Hospital, Karachi, Pakistan
#These authors contributed equally to this work.
Correspondence to: Syed Ather Enam, MD, PhD, FRCSI, FRCSC, FRCSG, FACS. Professor of Neurosurgery, Director, Centre of Oncological Research in Surgery, Scientific Director, Juma Research Laboratories, Aga Khan University Hospital, Stadium Road, P.O. Box 3500, Karachi 74800, Pakistan; Department of Surgery, Aga Khan University Hospital, Karachi, Pakistan. Email: ather.enam@aku.edu; Nouman Mughal, PhD. Assistant Professor, Department of Biological and Biomedical Sciences, Aga Khan University Hospital, Karachi, Pakistan; Centre of Oncological Research in Surgery, Aga Khan University Hospital, Stadium Road, P.O. Box 3500, Karachi 74800, Pakistan. Email: muhammad.nouman@aku.edu.
Background: Glioma prognosis remains a challenge due to its high recurrence and resistance to treatment. Diagnosis and follow-up in resource-constrained regions often lead to significant patient attrition. Serum microRNAs (miRNAs) are seen to be aberrantly expressed in malignancies can be found in tumor tissues and peripheral samples. This offers a pathway for non-invasive liquid biopsies. miR-21 is an established biomarker for glioma prognosis, which needs to be validated in our population.
Methods: We collected 89 intraoperative tumor tissue samples, and 42 pre- and post-operative serum samples from glioma patients, ten control tissues, eight healthy serum samples and analysed for miR-21 expression through quantitative polymerase chain reaction (qPCR) analysis. Correlational analysis with molecular markers isocitrate dehydrogenase (IDH), Ki-67, ATRX, p53, and survival curves through the Kaplan-Meier method were calculated in high and low miR-21 expression groups. The hazard ratio was quantitatively determined using Cox regression analysis, considering both univariate associations and multivariate correlations with clinical parameters.
Results: miR-21 expression in tissue was significantly upregulated with increase of glioma grades (P<0.001) and in patients above 50 years (P=0.003) age group. Whereas no gender bias was seen in its expression pattern. Its expression did not show any correlation with tumor volume (r=0.22, P=0.08). A similar expression pattern of miR-21 was observed in serum samples of glioma. IDH-wildtype (P=2.06e−03) and high Ki-67 (P=2.50e−03) patient group showed significant upregulation of miR-21 expression compared to IDH-mutant and low Ki-67 group. Patients with low miR-21 expression had significantly longer overall survival (OS) than patients with high miR-21 expression (P =0.006). Similarly, quantitative hazard analysis indicates that patients in the high expression group have 2.77 times higher risk of mortality [95% confidence interval (CI): 0.19–0.92], in comparison to patients in the low expression group (P=0.008).
Conclusions: Our findings validate the utility of miR-21 as a prognostic serum biomarker to help diagnose and assess treatment response in advancing glioma grades, within our population.
Keywords: Glioma; liquid biopsy; microRNAs (miRNAs); survival analysis; biomarker
