Review on Immunological Biomarkers in Gliomas

C. Nagalakshmi, N. Santhosh
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Abstract

Gliomas are the most common subgroup of primary malignant brain tumors in adults, constituting >40% of all primary CNS neoplasms. Although all gliomas originate from neuroepithelial tissues, they vary considerably in morphology, location, genetic alterations and in their response to therapy. The most malignant of gliomas (Grade IV) is Glioblastoma Multiforme (GBM), causing over 10,000 deaths each year in the US alone. Despite robust therapeutic advances, median survival for GBM still remains 14-20 months with very high tumor recurrence rate. Various investigation modalities are available for establishing diagnosis of glioma, like: CT scan, MRI, X-ray, spinal tap, angiogram, myelogram & biopsy, though, histopathology represents the gold standard for their typing & grading. However, even this remains unsatisfactory because of the lack of reproducibility and absence of precision. Development of objective, diagnostic, prognostic & predictive markers for these lethal neoplasms is therefore a priority. Biomarkers for glioma can be identified in various biological samples like: DNA, mRNA, cell surface receptors, transcription factors, secretory proteins, metabolites or processes such as proliferation, angiogenesis or apoptosis. Tumor biomarkers help oncologists in managing gliomas at various levels, from screening till assessment of longitudinal response to therapy. Identifying the molecular & pathogenetic characteristics of glioma regulation network may increase the precision of customized medication. Further, the proteomic approach has the potential to identify novel diagnostic, prognostic and therapeutic biomarkers. In the near future, improved proteomic profiling is anticipated to bring about a merger of biology, engineering and informatics, with a profound impact on glioma research and treatment. Optimization of experimental design and validation in independent cohorts, improved multiplex proteomic methodologies and bioinformatics tools, and their integration with genetic and metabolomic profiling technologies promise to play critical roles in the post proteomics era of cancer diagnosis and treatment.
胶质瘤免疫生物标志物研究进展
胶质瘤是成人原发性恶性脑肿瘤中最常见的亚群,占所有原发性中枢神经系统肿瘤的40%以上。虽然所有胶质瘤都起源于神经上皮组织,但它们在形态、位置、基因改变和对治疗的反应方面差异很大。最恶性的胶质瘤(IV级)是多形性胶质母细胞瘤(GBM),仅在美国每年就造成超过10,000人死亡。尽管治疗进展强劲,但GBM的中位生存期仍为14-20个月,肿瘤复发率非常高。胶质瘤的诊断有多种检查方式,如CT扫描、MRI、x线、脊髓穿刺、血管造影、骨髓造影和活检,但组织病理学是胶质瘤分型和分级的金标准。然而,由于缺乏可重复性和精确性,即使这样仍然不能令人满意。因此,开发这些致死性肿瘤的客观、诊断、预后和预测标志物是当务之急。胶质瘤的生物标志物可以在各种生物样品中识别,如:DNA, mRNA,细胞表面受体,转录因子,分泌蛋白,代谢物或增殖,血管生成或凋亡等过程。肿瘤生物标志物帮助肿瘤学家在不同水平上管理胶质瘤,从筛选到评估治疗的纵向反应。明确胶质瘤调控网络的分子及发病特点,可提高药物定制的精准度。此外,蛋白质组学方法具有鉴定新的诊断、预后和治疗生物标志物的潜力。在不久的将来,改进的蛋白质组学分析有望带来生物学,工程学和信息学的融合,对胶质瘤的研究和治疗产生深远的影响。在独立队列中优化实验设计和验证,改进多重蛋白质组学方法和生物信息学工具,以及它们与遗传和代谢组学分析技术的整合,有望在后蛋白质组学时代的癌症诊断和治疗中发挥关键作用。
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