Identification of Population-Specific Novel Protein Biomarkers and Possible Therapeutic Targets in Gliomas by Proteomics Approach

Objective To analyze the differential proteomic profile of gliomas in patients from South India and to identify novel protein glioma biomarkers and possible therapeutic targets to tailor the treatment to individual patients. Material and Methods We have prospectively analyzed the differential proteomic profile of 34 patients with glioma imaging characteristics and compared them with that of normal brain tissue. This research was conducted at the Institute of Neurosurgery, Madras Medical College, in technical collaboration with the Indian Institute of Technology, Madras, over 1 year. Statistical Analysis Biological variate analysis (I-ANALYSIS OF VARIANCE (ANOVA)) was used, with p-value less than 0.05 being significant. Results Twenty proteins (10 upregulated and 10 downregulated) were differentially expressed in tumor tissue. The expression of three pro-apoptotic proteins was downregulated and the expression of three anti-apoptotic proteins was upregulated with statistical significance. The cellular functions of the 20 differentially regulated proteins were subjected to pathway analysis revealing significant alterations in heme biosynthesis, deoxyribonucleic acid (DNA) replication, fibroblast growth factor (FGF) signaling, and epidermal growth factor (EGF0 receptor signaling in glioma. Conclusion KRT18, PRS4, and EF1A2 are anti-apoptotic proteins and are significantly upregulated in gliomas. EARS2, COX5A, and LSM3 are pro-apoptotic proteins, and are significantly downregulated in gliomas. This subverts the apoptotic pathways resulting in prolonged cell survival. This study's statistically significant dysregulation of these six proteins was unique, suggesting that they might be considered population-specific biomarkers and possible therapeutic targets for patients from South India. Abnormalities of heme biosynthesis at the proteomic level were identified in this study, which has not been very well studied previously.