Consequently, the 5-year survival rate for HCC following surgery is approximately 30–57% 12, 13, 14, 15, 16, 17, 18. However, because of complexities related to background liver status, the possibility of postoperative recurrence is higher in HCC, when compared with other gastrointestinal cancers. Although there are several recommended treatment options for HCC, surgical resection remains the most effective therapy for prolonging patient survival 11. The main risk factors for HCC include lifestyle factors such as heavy alcohol intake, obesity, smoking, type 2 diabetes, and aflatoxin-contaminated foodstuffs, as well as background liver status including chronic hepatitis B (HBV) or hepatitis C (HCV) viral infection and associated cirrhosis 7, 9, 10. Hepatocellular carcinoma (HCC) accounts for 75–85% of primary liver cancers and is the second leading cause of cancer-related death in East Asia and sub-Saharan Africa, and the sixth most common cause in Western countries 7, 8. Liver cancer is predicted to be the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related death worldwide 7. However, the relationship between circRNA expression and cancer prognosis requires further study. Recent studies have demonstrated abnormal circRNA expression in several types of malignancies 6. There is growing interest in the possible roles that circRNAs may play in the development of human diseases including malignant neoplasms. More recently, some circRNAs have been shown to encode proteins 6. circRNAs may also regulate gene expression directly by influencing transcription and splicing. It is believed that circRNA regulates gene expression through various interactions with other RNA types (e.g., as sponging microRNAs) as well as through interactions with RNA-binding proteins. While lncRNAs form the biggest group of mammalian ncRNAs, circular RNA (circRNA) is a recently identified subtype of lncRNA that demonstrates greater stability than linear RNA owing to its covalently closed loop structure 5. Long non-coding RNAs (lncRNAs) are ncRNAs that exceed 200 base pairs and they represent a relatively abundant component of the mammalian transcriptome 4. Many different ncRNAs have been identified to date and they are predominantly categorized according to length 3. Numerous studies have uncovered important functional roles for ncRNA in regulating the interplay between DNA, RNA and protein expression 2. Thus, there is an abundance of non-coding RNA (ncRNA) in the eukaryotic cell. Recent advances in genome-wide analytical techniques have revealed that while almost all genomic lesions are transferred into RNA, as little as 2% of these encode proteins 1. This study therefore identified circRNAs as potential prognostic markers for patients who undergo curative surgery for HCC and highlighted hsa_circ_0036683 as the most useful biomarker. There was no significant association between the expression of these circRNAs and hepatitis B/C status or cirrhosis. Additionally, multivariate analysis revealed that low hsa_circ_0036683 expression was a significant prognostic factor, independent from other clinicopathological features, for inferior RFS and OS. Kaplan–Meier analysis revealed that low expression of hsa_circ_0001020, hsa_circ_0036683, and hsa_circ_0058087 was associated with poor recurrence-free (RFS) and overall survival (OS) in HCC. The results of quantitative PCR showed that expression of hsa_circ_0041150, hsa_circ_0001020 and hsa_circ_0008558 was significantly lower in HCC than in background normal liver tissues. The expression of these circRNAs was examined by quantitative PCR in 233 sets of HCC and matched background normal liver tissues, and correlations between candidate circRNA expression and prognosis were evaluated. circRNA has promise as a cancer-related biomarker because its circular structure affords high stability. Circular RNA (circRNA) is a type of non-coding RNA known to affect cancer-related micro RNAs and various transcription factors.
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