Identification of Potential Biomarkers of Platelet RNA in Glioblastoma by Bioinformatics Analysis

Abstract

Objective. Glioblastoma is one of the most common and fatal malignancies in adults. Current treatment is still not optimistic. Glioblastoma (GBM) transports RNA to platelets in the blood system via microvesicles, suggesting that platelet RNA can be a potential diagnostic and therapeutic target. The roles of specific platelet RNAs in treatment of GBM are not well understood. Methods. Platelet RNA profiling of 8 GBM and 12 normal samples were downloaded from the GEO database. Differentially expressed genes (DEGs) were identified between tumors and normal samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the functions of up- and downregulated genes. miRNA was predicted by miRTarBase, TargetScan, and miRDB databases. circBase and circBank were used for circRNA prediction. ceRNA (circRNA-mRNA-miRNA) network was constructed to investigate the potential interactions. Results. 22 genes were upregulated and 9 genes were downregulated. There are only two genes (CCR7 and FAM102A) that connect to miRNAs (hsa-let-7a-5p, hsa-miR-1-3p). We assessed the overall survival rates by Kaplan-Meier plotter, and relative expression of GBM and subtypes for overlapped mRNA (CCR7 and FAM102A) were evaluated, and further, we obtained circRNAs (has-circ-0015164, hsa-circ-0003243) by circBank and circBase and bind sites through the CSCD database. Finally, a ceRNA network (circRNA-mRNA-miRNA) was constructed based on 2 miRNAs, 2 mRNAs, and 2 circRNAs by Cytoscape. This study focused on potential mRNA and ceRNA biomarkers to targeted treatment of GBM and provided ideas for clinical treatment through the combination of hematology and oncology. Conclusion. The findings of this study contribute to better understand the relationship between GBM and the blood system (platelets) and might lay a solid foundation for improving GBM molecule and gene diagnosis and prognosis.

Systemic Inflammatory Indices in Patients With Malignant Gliomas and Effects of Platelet Secretome in Vitro

“…TME also modulates the Pt function, directly inducing Pt aggregation with tumor cells and triggering the release of granules. At the same time, Pts absorb and transport tumor EXs with mutant RNA, and also actively and effectively release protumor EXs, contributing to tumor spread [31,35,36]. The so-called "tumor-educated" Pts have an altered mRNA profile [34,35] and an increased content of angiogenesis regulatory proteins (VEGF, PDGF, bFGF) [42].…”

“…At the same time, Pts absorb and transport tumor EXs with mutant RNA, and also actively and effectively release protumor EXs, contributing to tumor spread [31,35,36]. The so-called "tumor-educated" Pts have an altered mRNA profile [34,35] and an increased content of angiogenesis regulatory proteins (VEGF, PDGF, bFGF) [42]. They enhance the dissemination of tumor cells, activating the function of endotheliocytes and recruiting immunocytes to primary and metastatic tumors [43].…”

“…When infiltrating tumor tissue [30], Pts, in addition to containing numerous granules with mediators of protumoral, angiogenic action [17,27,31], are also able to absorb, transport, and release EXs with tumorassociated RNA and, thus, be involved in various stages of tumor emergence and progression [32]. Tumor cells can directly and/or indirectly influence the RNA content in Pt [33]: in so-called "tumor-edu cated platelets", the mRNA repertoire changes [34,35]. Tumor cells, through the release of EXs, transfer mutant RNA to Pts, which absorb and transport them [31,35], promoting the spread of tumor RNA through the bloodstream, and Pts efficiently release protumor EXs, which provides a tumor survival "strategy", as suggested by some authors [36].…”

“…Tumor cells can directly and/or indirectly influence the RNA content in Pt [33]: in so-called "tumor-edu cated platelets", the mRNA repertoire changes [34,35]. Tumor cells, through the release of EXs, transfer mutant RNA to Pts, which absorb and transport them [31,35], promoting the spread of tumor RNA through the bloodstream, and Pts efficiently release protumor EXs, which provides a tumor survival "strategy", as suggested by some authors [36]. Thus, the study of the Pt properties in patients with brain MG is of particular importance.…”

Circulating circRNA: a social butterfly in tumors

“…CircNRIP1, which was downregulated in the NSCLC group, could be employed as a potential biomarker for NSCLC (37). Chen et al analyzed the platelet RNA profiles of 8 glioblastoma samples and 12 normal samples and constructed a ceRNA network (circRNA-mRNA −miRNA) based on 2 miRNAs (hsa-let-7a-5p, hsa-miR-1-3p), 2 mRNAs (CCR7 and FAM102A), and 2 circRNAs (has-circ-0015164, hsa-circ-0003243) to investigate the potential interactions (32). This study also sheds light on the potential relationship between platelet circRNAs and cancer, as well as the clinical value of platelet circRNAs.…”