Serum-derived three-circRNA signature as a diagnostic biomarker for hepatocellular carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) is a common tumor characterized by high morbidity and mortality rates. The importance of circRNA in cancer diagnosis has been established. The study aimed to identify differentiallyexpressed circRNAs (DECs) in human blood exosomes from patients with HCC and to investigate their diagnostic value. Methods: The circRNA expression profiles of HCC and normal human blood samples were downloaded and processed from the exoRBase database. At the cutoff criteria of a fold change (FC) > 2.0 and P < 0.05, DECs were screened utilizing the limma package in the R software. A receiver operator characteristic curve (ROC) was used to study its diagnostic value. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis was performed to confirm the three-circRNAs expression in the blood samples with HCC. Various bioinformatics tools were used to characterize the potential biological pathways induced by circRNAs. Results: Compared with the normal samples, seven up-regulated and five down-regulated circRNAs were determined in the HCC samples. ROC analyses demonstrated that hsa_circ_0004001, hsa_circ_0004123, hsa_circ_0075792, and a combination of the three biomarkers exhibited higher sensitivity and specificity. The qRT-PCR confirmed that the three circRNAs were upregulated in the blood samples with HCC. Chi squared tests implied that the expression of three circRNAs was positively correlated with the TNM stage and tumor size. The circRNAs participated in VEGF/VEGFR, PI3K/Akt, mTOR, and Wnt signaling pathways by targeting miRNAs. Conclusions: The study established the existence of seven up-regulated and five down-regulated circRNAs in HCC. Additionally, hsa_circ_0004001, hsa_circ_0004123, hsa_circ_0075792, and a combination of the three were utilized as valuable diagnostic biomarkers in HCC.

Circulating Long and Circular Noncoding RNA as Non-Invasive Diagnostic Tools of Hepatocellular Carcinoma

“…Despite this study being performed in whole serum RNA extracts, consistency was found with the data retrieved from the exoRBase database [109] (http://www.exorbase.org/exoRBase/toIndex), which include exosomal circRNAs from 21 HCC patients. Indeed, the diagnostic potential of these three candidates was also verified through ROC curve analysis, showing the discriminatory potential of the circRNAs between HCC patients and controls with an AUC always above 0.70 [65].…”

The Latest Overview of circRNA in the Progression, Diagnosis, Prognosis, Treatment, and Drug Resistance of Hepatocellular Carcinoma

“…Sun et al. ( 81 ) report that hsa_circ_0004001, hsa_circ_0004123 and hsa_circ_0075792 are upregulated in the blood samples of HCC. ROC analysis shows that the AUC value of the combination of the three circRNAs is 0.89, indicating that the combination of the three circRNAs could be a potential diagnostic biomarker in HCC.…”

Circular RNAs and Hepatocellular Carcinoma: New Epigenetic Players With Diagnostic and Prognostic Roles

“…By analyzing differentially expressed circRNAs (DECs) in plasma between 40 healthy controls and 71 HCC patients, Sun et al recently identified a three-circRNA signature, including hsa_circ_0004001, hsa_circ_0004123, and hsa_circ_0075792, which are highly expressed in HCC patients (50). This 3-circRNA signature showed a potent diagnosis value (AUC: 0.89, sensitivity: 0.905; specificity: 0.781) (50).…”

“…By analyzing differentially expressed circRNAs (DECs) in plasma between 40 healthy controls and 71 HCC patients, Sun et al recently identified a three-circRNA signature, including hsa_circ_0004001, hsa_circ_0004123, and hsa_circ_0075792, which are highly expressed in HCC patients (50). This 3-circRNA signature showed a potent diagnosis value (AUC: 0.89, sensitivity: 0.905; specificity: 0.781) (50). In this study, the authors did not compared the diagnosis value of the 3-circRNA signature with that of AFP, but the AUC, sensitivity and specificity values of the 3-circRNA signature may slightly better than those of AFP from other studies (48,49).…”