Molecular Diagnostic Biomarkers in Brain Cancer: Exploring miRNAs and Proteins in Blood and CSF

Brain cancers remain among the most challenging malignancies to diagnose and treat due to the complexity of the blood-brain barrier (BBB). This is especially true for glioblastoma, the most common and aggressive primary malignant tumor arising from the central nervous system (CNS). These challenges have led researchers to focus on identifying efficient molecular diagnostic biomarkers. In this study, we investigate different brain cancer types based on the ۲۰۲۱ WHO Classification of Tumors of the Central Nervous System, including diffuse gliomas such as astrocytomas (including glioblastoma), oligodendrogliomas, and other glioma subtypes. We examined tumors across different WHO grades, from lower-grade (WHO grade ۲) to higher-grade (WHO grade ۳ and ۴) gliomas, seeking to identify specific molecular signatures that could aid in diagnosis and prognostication. Our research focuses on the emerging role of microRNAs (miRNAs) and proteins as promising biomarkers in brain cancer diagnosis and prognosis. miRNAs, small non-coding RNAs that regulate gene expression, have a significant impact on diseases and cellular health due to their wide range of functions and targets. We observed differential expression patterns of miRNAs in various brain cancer types. Notable examples include upregulated miRNAs such as miR-۲۱, miR-۱۰b, and miR-۱۹۶a, which are frequently elevated in GBM, the most aggressive form of brain cancer. Conversely, miR-۱۲۸, miR-۱۲۴, and miR-۱۳۷ were found to be downregulated in these tumors. In addition to miRNAs, we identified several protein biomarkers demonstrating significant diagnostic and prognostic value. Heat shock proteins Hsp۷۰ and Hsp۱۱۰ were found to indicate disease progression. Bcl-۲ showed association with early-stage cancer, while BCAS۱ and INF۲ were identified as upregulated proteins in certain brain cancer types. Critically, we investigated the feasibility of detecting these biomarkers in both blood and cerebrospinal fluid (CSF) samples. Many miRNAs were detectable in both biofluids, offering potential for minimally invasive diagnostic and monitoring approaches. Specifically, miR-۲۱, miR-۱۰b, and miR-۱۹۶a, frequently upregulated in GBM, were detectable in both blood and CSF samples. However, the concentrations and reliability of detection varied between the two biofluids. CSF generally provided higher sensitivity and specificity for brain cancer-specific miRNAs due to its proximity to the tumor site and the blood-brain barrier's filtering effect. Our findings suggest that a combined approach, using blood tests for initial screening and CSF analysis for confirmation and detailed monitoring, might provide the most comprehensive assessment. This strategy could potentially overcome current diagnostic challenges and pave the way for personalized diagnostic strategies in brain cancer. In conclusion, our study highlights the potential of miRNA and protein biomarkers in improving brain cancer diagnosis and monitoring. Future research should focus on validating these biomarkers in larger clinical cohorts and exploring their potential as therapeutic targets. The integration of these molecular biomarkers into clinical practice holds promise for enhancing early detection, improving prognostic accuracy, and guiding personalized treatment strategies in brain cancer management.

کلیدواژه ها:

Brain Cancer ، Diagnostic Biomarker ، miRNA ، Protein ، Glioblastoma