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

IF 0.3 Q4 SURGERY Indian Journal of Neurosurgery Pub Date : 2024-05-17 DOI:10.1055/s-0044-1786983

S. Devanand Senthil Kumar, Anbazhagan Periyasamy

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Abstract

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.

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用蛋白质组学方法鉴定胶质瘤中群体特异性新型蛋白质生物标记物和可能的治疗靶点

目的分析南印度胶质瘤患者的不同蛋白质组学特征，并确定新的胶质瘤蛋白质生物标记物和可能的治疗靶点，以便根据患者的具体情况进行治疗。材料与方法我们前瞻性地分析了 34 名具有胶质瘤成像特征的患者的不同蛋白质组谱，并将其与正常脑组织的蛋白质组谱进行了比较。这项研究是在马德拉斯医学院神经外科研究所与马德拉斯印度理工学院的技术合作下进行的，历时一年。统计分析采用生物变量分析法（I-ANALYSIS OF VARIANCE (ANOVA)），P 值小于 0.05 为显著。结果 20 种蛋白质（10 种上调，10 种下调）在肿瘤组织中有差异表达。其中三个促凋亡蛋白表达下调，三个抗凋亡蛋白表达上调，差异有统计学意义。对这 20 个差异调控蛋白的细胞功能进行通路分析后发现，胶质瘤中的血红素生物合成、脱氧核糖核酸（DNA）复制、成纤维细胞生长因子（FGF）信号转导和表皮生长因子（EGF0）受体信号转导发生了显著变化。结论 KRT18、PRS4 和 EF1A2 是抗凋亡蛋白，在胶质瘤中显著上调。EARS2、COX5A 和 LSM3 是促凋亡蛋白，在胶质瘤中明显下调。这就破坏了凋亡途径，导致细胞存活时间延长。这项研究在统计学上发现这六种蛋白质的明显失调是独一无二的，这表明它们可被视为人群特异性生物标志物和南印度患者的可能治疗靶点。本研究发现了蛋白质组水平上的血红素生物合成异常，而这在以前还没有得到很好的研究。

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