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

Circular RNA Sequencing Reveals Serum Exosome Circular RNA Panel for High-Grade Astrocytoma Diagnosis.

机构信息

NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, China, Cancer Research Institute, Central South University, Changsha, Hunan 410008, China.

出版信息

Clin Chem. 2022 Feb 1;68(2):332-343. doi: 10.1093/clinchem/hvab254.

DOI:10.1093/clinchem/hvab254

PMID:34942001

Abstract

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.

摘要

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，但有效的非侵入性诊断方法仍知之甚少。外泌体可以穿过血脑屏障，并且在人体生物流体中容易获得，因此它们是 HGA 的有前途的生物标志物。由于其稳定性、保守性和组织特异性，环状 RNA（circRNA）具有作为肿瘤生物标志物的潜力。然而，HGA 中外泌体 circRNA 的全景和特征仍有待研究。

方法

使用 circRNA 深度测序和生物信息学方法生成 circRNA 图谱数据库，并分析 HGA 细胞 circRNA 和 HGA 细胞衍生的外泌体 circRNA 的特征。使用逆转录定量 PCR 检测健康个体和 HGA 患者血清和组织中外泌体 circRNA 的表达。此外，还分析了接收者操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 细胞更有可能富集短外显子和抑制性 circRNA。此外，包括 hsa_circ_0075828、hsa_circ_0003828 和 hsa_circ_0002976 的血清外泌体 circRNA 谱可用于筛选 HGA，而包含高浓度 hsa_circ_0005019、hsa_circ_0000880、hsa_circ_0051680 和 hsa_circ_0006365 的良好预后谱组成。