Background Although major advances have been made in the histopathological diagnosis of high-grade astrocytoma (HGA), methods for effective and noninvasive diagnosis remain largely unknown. Exosomes can cross the blood–brain barrier and are readily accessible in human biofluids, making them promising biomarkers for HGA. Circular RNAs (circRNAs) have potential as tumor biomarkers owing to their stability, conservation, and tissue specificity. However, the landscape and characteristics of exosome circRNAs in HGA remain to be studied. Methods CircRNA deep sequencing and bioinformatics approaches were used to generate a circRNA profiling database and analyze the features of HGA cell circRNAs and HGA cell-derived exosome circRNAs. Exosome circRNA expression in the serum and tissues of healthy individuals and patients with HGA was detected using reverse transcription-quantitative PCR. Additionally, the receiver operating characteristic curve and overall survival curves were analyzed. Results By investigating the characteristics of HGA cell-derived exosome circRNAs and HGA cell circRNAs, we observed that exosomes were more likely to enrich short-exon and suppressor circRNAs than HGA cells. Moreover, a serum exosome circRNA panel including hsa_circ_0075828, hsa_circ_0003828, and hsa_circ_0002976 could be used to screen for HGA, whereas a good prognosis panel comprised high concentrations of hsa_circ_0005019, hsa_circ_0000880, hsa_circ_0051680, and hsa_circ_0006365. Conclusions This study revealed a comprehensive circRNA landscape in HGA exosomes and cells. The serum exosome circexosome circRNA panel and tissue circRNAs are potentially useful for HGA liquid biopsy and prognosis monitoring. Exosome circRNAs as novel targets should facilitate further biomarker discovery and aid in HGA diagnosis and therapy monitoring.

中文翻译：

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环状 RNA 测序揭示了用于高级星形细胞瘤诊断的血清外泌体环状 RNA 面板

背景 尽管在高级别星形细胞瘤 (HGA) 的组织病理学诊断方面取得了重大进展，但有效和无创诊断的方法仍然很大程度上未知。外泌体可以穿过血脑屏障并且在人体生物体液中很容易获得，这使得它们成为 HGA 的有希望的生物标志物。环状 RNA (circRNA) 因其稳定性、保守性和组织特异性而具有作为肿瘤生物标志物的潜力。然而，HGA 中外泌体 circRNA 的景观和特征仍有待研究。方法利用CircRNA深度测序和生物信息学方法构建circRNA profiling数据库，分析HGA细胞circRNA和HGA细胞来源的外泌体circRNA的特征。使用逆转录定量 PCR 检测健康个体和 HGA 患者血清和组织中的外泌体 circRNA 表达。此外，还分析了受试者工作特征曲线和总生存曲线。结果 通过研究 HGA 细胞衍生的外泌体 circRNA 和 HGA 细胞 circRNA 的特征，我们观察到外泌体比 HGA 细胞更可能富集短外显子和抑制 circRNA。此外，包括 hsa_circ_0075828、hsa_circ_0003828 和 hsa_circ_0002976 的血清外泌体 circRNA panel 可用于筛查 HGA，而良好预后 panel 包括高浓度的 hsa_circ_0005019、hsa_circ_0000880、hsa_circ_0051680 和 hsa_circ_0006365。结论 本研究揭示了 HGA 外泌体和细胞中的全面 circRNA 格局。血清外泌体 circexosome circRNA panel 和组织 circRNA 可能对 HGA 液体活检和预后监测有用。作为新靶点的外泌体 circRNA 应有助于进一步发现生物标志物并有助于 HGA 诊断和治疗监测。