Circular RNAs in Diagnosis of Astrocytoma
Original author: Peiyao Li, Zihao Xu, et. al. (2022) (DOI: 10.1093/clinchem/hvab254)
Sr. scientist – Omics
March 01, 2023
Astrocytoma is a type of brain tumor associated with astrocytes. Grade IV astrocytoma is commonly known as glioblastoma. Molecular-based diagnosis is challenging as it requires brain surgery for obtaining tissue samples/specimens from the tumor site. On the other hand, circular RNA (circRNAs) are abundant in the brain tissues, and their expression level changes with neural development. They are carried by exosomes which can cross the blood-brain barrier. CircRNAs are also found in biofluids, which are easily accessible, and hence a potential candidate for liquid biopsy. The current research article looks for the possible circRNAs as biomarkers of high-grade astrocytoma (HGA).
Cells were collected from grade IV glioma patients. CircRNAs in tumor cells and tumor cell-derived exosomes were compared in three pairs. CircRNAs from the tissues and serum of high-grade glioma (HGA) patients were compared with tissues and serum of healthy individuals.
Exosomes were isolated following protocols. CircRNAs were isolated, amplified, and sequenced. The reads were aligned with the reference genome and compared with the circbase database to identify the known and predicted circRNAs.
This study shows cells are more populated with circRNAs compared to cell-derived exosomes. Twenty-six highly expressed circRNAs coexisted in all three tumor cells and 12 circRNAs were commonly enriched in three tumor cell-derived exosomes. 11 higher level HGA cell-derived exosome circRNAs were included in the HGA cell circRNAs. There are five higher-level cell circRNAs across all samples. Among them, three circRNAs were highly expressed in both HGA cells and exosomes. Randomly chosen circRNAs show low expression levels in tumor tissues compared to the tissues from healthy individuals and eight circRNAs show significant differences in the expression levels. Among them, four are associated with overall survival, and hence can be used as biomarkers.
Serum exosome circRNAs from HGA patients and healthy individuals were compared. Thirteen (nine up and four down) circRNAs were significantly different and three of them had significantly different expression levels. Any two of these can distinguish normal and HGA patients and can be used as biomarkers for liquid biopsy.
Down-regulation of most of the differentially expressed circRNAs was observed in HGA tissues and HGA serum exosomes compared to their normal counterpart. Most of the reduced circRNAs are involved in glioma formation and development. This study identifies three serum exosome circRNAs that could form a panel of noninvasive liquid biomarkers for the precise screening of HGA.
There are several challenges. The current study aims to develop circRNAs research technology. It is difficult to accurately extract the sequence and length of intronic circRNA through software.
This study characterizes HGA cell circRNAs and exosome circRNAs. A serum exosome panel of 3 circRNAs was identified as biomarkers. Tissue circRNAs can serve as tissue biopsy targets for monitoring HGA prognosis.
Impact of the research
This study identifies novel issues in the fields of HGA, exosome, and circRNA research, providing new directions for future studies. It enhances the potential of liquid biopsy which may help diagnose cancers at sites where accessing tissue is difficult.