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Serum-derived three-circRNA signature as a diagnostic biomarker for hepatocellular carcinoma
Xiang-Hong Sun1, Yu-Tong Wang2, Guo-Fu Li1
1Department of Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
Insights
This study identified seven up-regulated and five down-regulated circular RNAs (circRNAs) in hepatocellular carcinoma (HCC) blood exosomes. Three specific circRNAs (hsa_circ_0004001, hsa_circ_0004123, hsa_circ_0075792) show promise as diagnostic biomarkers for HCC.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Hepatocellular carcinoma (HCC) presents significant global health challenges due to high mortality rates.
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer development and as potential diagnostic markers.
- Exosomes derived from blood offer a non-invasive source for identifying cancer biomarkers.
Purpose of the Study:
- To identify differentially-expressed circRNAs (DECs) in blood exosomes from HCC patients.
- To evaluate the diagnostic potential of identified DECs in distinguishing HCC from healthy individuals.
- To explore the biological pathways potentially regulated by these DECs in HCC.
Main Methods:
- circRNA expression profiles were analyzed from the exoRBase database for HCC and normal samples.
- Differential expression analysis (fold change > 2.0, P < 0.05) was performed using the limma package in R.
- Receiver operator characteristic (ROC) curve analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were employed for diagnostic validation.
Main Results:
- Seven circRNAs were upregulated and five were downregulated in HCC blood exosomes compared to controls.
- ROC analysis indicated high diagnostic accuracy for hsa_circ_0004001, hsa_circ_0004123, hsa_circ_0075792, and their combination.
- qRT-PCR confirmed the upregulation of these three circRNAs in HCC patients, correlating with TNM stage and tumor size.
Conclusions:
- The study successfully identified specific circRNAs in HCC blood exosomes with diagnostic potential.
- hsa_circ_0004001, hsa_circ_0004123, and hsa_circ_0075792, individually or combined, serve as promising non-invasive biomarkers for HCC diagnosis.
- These circRNAs are implicated in key signaling pathways (VEGF/VEGFR, PI3K/Akt, mTOR, Wnt) relevant to cancer progression.
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 differentially-expressed 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.
