• Biomarker
• Cancer
• Therapy
• circRNA

• Humans
• RNA, Circular/genetics
• RNA, Circular/metabolism
• Neoplasms/genetics
• Neoplasms/therapy
• Neoplasms/diagnosis
• Biomarkers, Tumor/metabolism
• Biomarkers, Tumor/genetics
• Animals
• Gene Expression Regulation, Neoplastic

• 82072662 National Natural Science Foundation of China
• 2019142 Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support
• SHDC2020CR4022 Shanghai Three-year Action Plan to Promote Clinical Skills and Clinical Innovation in Municipal Hospitals

• Biomedical applications
• Database
• Strategy
• Therapeutic approaches
• circRNA

• 2022YFA1300020 National Key Research and Development Program of China
• 2021YFA1300502 National Key Research and Development Program of China
• 2019JC05N394 Natural Science Foundation of Guangdong Province
• 2021B1515020002 Natural Science Foundation of Guangdong Province
• 32170570 National Natural Science Foundation of China
• 231gbj010 Sun Yat-sen University

• Circular RNA 0001789
• Epithelial-mesenchymal transition
• Gastric cancer
• MicroRNA-140-3p
• p21 activated kinase 2

• Biomarkers
• Circular RNAs
• Diagnosis
• Function
• Hepatocellular carcinoma
• Targeted therapy

The incidence of hepatocellular carcinoma (HCC) is increasing worldwide. Extracellular vesicles (EVs) contain sufficient bioactive substances and are carriers of intercellular information exchange, as well as delivery vehicles for nucleic acids, proteins and drugs. Although EVs show great potential for the treatment of HCC and their role in HCC progression has been extensively studied, there are still many challenges such as time-consuming extraction, difficult storage, easy contamination, and low drug loading rate. We focus on the biogenesis, morphological characteristics, isolation and extraction of EVs and their significance in the progression of HCC, tumor invasion, immune escape and cancer therapy for a review. EVs may be effective biomarkers for molecular diagnosis of HCC and new targets for tumor-targeted therapy.

• extracellular vesicles
• hepatocellular carcinoma
• hypoxia
• tumor microenvironment
• vesicle drug delivery

Circular RNA (circRNA), a new type of endogenous non-coding RNA, is abundantly present in eukaryotic cells, and characterized as stable high conservation and tissue specific expression. It has been generated increasing attention because of their close association with the progress of diseases. The liver is the vital organ of humans, while it is prone to acute and chronic diseases due to the influence of multiple pathogenic factors. Moreover, hepatocellular carcinoma (HCC) is the one of most common cancer and the leading cause of cancer death worldwide. Overwhelming evidences indicate that some circRNAs are differentially expressed in liver diseases, such as, HCC, chronic hepatitis B, hepatic steatosis and hepatoblastoma tissues, etc. Additionally, these circRNAs are related to proliferation, invasion, migration, angiogenesis, apoptosis, and metastasis of cell in liver diseases and act as oncogenic agents or suppressors, and linked to clinical manifestations. In this review, we briefly summarize the biogenesis, characterization and biological functions, recent detection and identification technologies of circRNA, and regulation network mechanism of circRNA in liver diseases, and discuss their potential values as biomarkers or therapeutic targets for liver diseases, especially on HCC.

• Biomarker
• Hepatocellular carcinoma (HCC)
• Liver diseases
• circRNA
• miRNA sponge

• ASO, antisense oligonucleotide
• CCA, cholangiocarcinoma
• CLIP, cross-linking immunoprecipitation
• EMT, epithelial-to-mesenchymal transition
• EVs, extracellular vesicles
• HCC, hepatocellular carcinoma
• HN1, haematopoietic- and neurologic-expressed sequence 1
• IRES, internal ribosome entry sites
• NGS, next-generation sequencing
• QKI, Quaking
• RBP, RNA-binding protein
• RISC, RNA-induced silencing complex
• TAM, tumour-associated macrophage
• TSB, target site blockers
• biomarker
• cancer hallmarks
• cholangiocarcinoma
• circRNA
• circRNA, circular RNA
• hepatocellular carcinoma
• miRNA, microRNA
• shRNA, small-hairpin RNA
• snRNP, small nuclear ribonuclear proteins

The lack of accurate biomarkers impeded the screening, diagnosis and early treatment of hepatocellular carcinoma (HCC). As a result of the development of high-throughput transcriptome analysis techniques, circular RNAs, a newly discovered class of noncoding RNAs, were recognized as potential novel biomarkers. This meta-analysis was performed to update the diagnostic roles of circular RNAs for HCC. We acquired 23 articles from PubMed, Web of Science, EMBASE, and Cochrane Library databases up to September 2021. The overall sensitivity was 0.80 (95% CI: 0.77–0.84), and the specificity was 0.83 (95% CI: 0.79–0.85), with an AUC of 0.88 (0.85–0.91). Considering of the significant heterogeneity, studies were divided into four groups based on the control types. The circular RNAs in exosomes had a sensitivity of 0.69 (95% CI: 0.61–0.75), and a highest specificity of 0.91 (95% CI: 0.83–0.96). The pooled sensitivity of circular RNAs in serum/plasma was 0.84 (95% CI: 0.81–0.87), and the pooled specificity was 0.83 (95% CI: 0.79–0.86). The pooled sensitivity of circular RNAs distinguishing tumor tissue from chronic hepatitis/cirrhosis tissues was 0.56 (95% CI: 0.48–0.64), and specificity was 0.76 (95% CI: 0.67–0.82). When the controls were adjacent tissues, the sensitivity was 0.78 (95% CI: 0.70–0.84), and the specificity was 0.78 (95% CI: 0.71–0.85). Hsa_circ_0001445 with a pooled sensitivity of 0.81, a specificity of 0.76 and an AUC of 0.85 in two studies, might be a suitable diagnostic blood biomarker for HCC. Relying on function in HCC, the AUC of subgroups were 0.88 (95%CI: 0.84–0.90) (function group) and 0.87 (95%CI: 0.84–0.90) (unknown function group). As for only reported in HCC or not, these circular RNAs had an AUC of 0.89 (95%CI: 0.86–0.91) (only in HCC) and 0.85 (95%CI: 0.82–0.88) (not only in HCC). In conclusion, the results suggested that circular RNAs were acceptable biomarkers for detecting HCC, especially those circular RNAs existing in exosomes or serum/plasma.

• circular RNAs
• diagnosis
• exosome
• hepatocellular carcinoma
• meta-analysis
• serum/plasma

Cancer stemness, mainly consisting of chemo-resistance, radio-resistance, tumorigenesis, metastasis, tumor self-renewal, cancer metabolism reprogramming, and tumor immuno-microenvironment remodeling, play crucial roles in the cancer progression process and has become the hotspot of cancer research field in recent years. Nowadays, the exact molecular mechanisms of cancer stemness have not been fully understood. Extensive studies have recently implicated that non-coding RNA (ncRNA) plays vital roles in modulating cancer stemness. Notably, N6-methyladenosine (m6A) modification is of crucial importance for RNAs to exert their biological functions, including RNA splicing, stability, translation, degradation, and export. Emerging evidence has revealed that m6A modification can govern the expressions and functions of ncRNAs, consequently controlling cancer stemness properties. However, the interaction mechanisms between ncRNAs and m6A modification in cancer stemness modulation are rarely investigated. In this review, we elucidate the recent findings on the relationships of m6A modification, ncRNAs, and cancer stemness. We also focus on some key signaling pathways such as Wnt/β-catenin signaling, MAPK signaling, Hippo signaling, and JAK/STAT3 signaling to illustrate the underlying interplay mechanisms between m6A modification and ncRNAs in cancer stemness. In particular, we briefly highlight the clinical potential of ncRNAs and m6A modifiers as promising biomarkers and therapeutic targets for indicating cancer stemness properties and improving the diagnostic precision for a wide variety of cancers.

• N6-methyladenosine (m6A) modification
• biomarkers
• cancer stemness
• non-coding RNA (ncRNA)
• signaling pathways

• Biomarker
• Expression
• Hepatocellular carcinoma
• circRNA

• AML, acute myloid leukemia
• BSJ, back-splice junction
• Biomarker
• CLL, chronic lymphocytic leukemia
• CML, chronic myeloid leukemia
• CRC, colorectal cancer
• Cancer
• Circular RNAs
• EIciRNAs, exon–intron RNAs
• EMT, epithelial-mesenchymal transition
• Functions
• GC, gastric cancer
• HCC, hepatocellular carcinoma
• ISH, in situ hybridization
• LUAD, lung adenocarcinoma
• MER, miRNA response elements
• MM, multiple myeloma
• NSCLC, non-small cell lung cancer
• PCR, polymerase chain reaction
• PDAC, pancreatic ductal adenocarcinoma
• RBP, RNA-binding protein
• RNA, ribonucleic acid
• RNase, ribonuclease
• RT-PCR, reverse transcription-PCR
• TNM, tumor node metastases
• UTR, untranslated regions
• ccRCC, clear cell renal cell carcinoma
• ceRNAs, endogenous RNAs
• ciRNAs, circular intronic RNAs
• ciRS-7, circular RNA sponge for miR-7
• circRNAs, circular RNAs
• ecircRNAs, exonic circular RNAs
• lncRNAs, long ncRNA
• miRNAs, microRNAs
• ncRNAs, noncoding RNAs
• qPCR, quantitative PCR
• rRNA, ribosomal RNA
• siRNAs, small interfering RNAs
• snRNA, small nuclear RNA
• tricRNAs, tRNA intronic circRNAs

Circular RNA (circRNA) is a novel subclass of noncoding-RNA molecules that participate in development and progression of a variety of human diseases via sponging microRNAs (miRNAs). Until now, the contributions of circRNAs in chemoresistance of hepatocellular carcinoma (HCC) remain largely unknown. In the present study, we aimed to investigate the role of circRNA in cisplatin resistance of HCC. We investigated the expression of circRNAs in 5 paired cisplatin-sensitive and cisplatin-resistant HCC tissues by microarray analysis. The qRT-PCR analysis was to investigate the expression pattern of circARNT2 in HCC patient tissues and cell lines. Then, the effects of circARNT2 on cisplatin resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo. circARNT2 was significantly upregulated in HCC tissues and cell lines. Overexpression of circARNT2 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. In vitro experiments showed that knockdown of circARNT2 inhibited cell proliferation and enhances the cisplatin sensitivity of HCC cells. Furthermore, circARNT2 facilitates HCC progression in vivo. We demonstrated that circARNT2 acts as a sponge for miR-155-5p and verified that PDK1 is a novel target of miR-155-5p. In summary, our study demonstrated that circARNT2 modulates cisplatin resistance through miR-155-5p/PDK1 pathway. Our findings indicated that circARNT2 may serve as a promising therapeutic target for overcoming cisplatin resistance for HCC.

• HCC
• ceRNA
• chemoresistance
• circARNT2
• circRNA
• cisplatin
• miR-155-5p

Mounting evidences indicate that circular RNAs (circRNAs) play vital roles in the development and progression of various cancers. However, the detailed functions and underlying mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain largely unknown. The expression profile of circRNAs was screened by circRNA microarrays. Quantitative real-time PCR was used to determine the level-10 circRNAs selected from the top five upregulated (hsa_circ_0001955, hsa_circ_0001535, hsa_circ_0061395, hsa_circ_0000502, and hsa_circ_0066659) and top five downregulated circRNAs (hsa_circ_0046366, hsa_circ_0003418, hsa_circ_0026134, hsa_circ_0005692, and hsa_circ_0014130). The effects of circTMEM45A in HCC cells were studied both in vitro (in a Cell Counting Kit-8 assay, apoptosis analysis, and cell cycle assays) and in vivo (by means of tumor xenografts in nude mice). Luciferase reporter, RNA immunoprecipitation (RIP), and rescued assays were used to confirm the interactions between circTMEM45A, miR-665, and insulin growth factor 2 (IGF2). We found that the level of circTMEM45A was significantly upregulated in HCC and was positively correlated with clinicopathological features and poor prognosis of patients with HCC. Functionally, circTMEM45A promoted cell mobility in vitro, as well as in vivo tumorigenesis. Mechanistically, circTMEM45A acted as a miR-65 sponge to relieve the repressive effect of miR-665 on its target IGF2. Moreover, circTMEM45A was upregulated in serum exosomes from HCC patients. circTMEM45A promotes HCC progression through the miR-665/IGF2 axis and may serve as a novel diagnostic marker and target for treatment of HCC patients.

• IGF2
• circTMEM45A
• exosome
• hepatocellular carcinoma
• miR-665

• biological markers
• carcinoma, hepatocellular
• gene expression

• Biomarkers, Tumor/metabolism
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• MicroRNAs/metabolism
• Neoplasm Invasiveness/genetics
• Neoplasm Metastasis/genetics
• Prognosis
• RNA, Circular/metabolism
• RNA, Circular/physiology
• RNA-Binding Proteins/metabolism

• biomarkers
• circular RNAs
• exosome
• gastrointestinal malignancies
• non-invasive diagnosis

• Biomarkers, Tumor/genetics
• Carcinoma, Hepatocellular/genetics
• Exosomes/genetics
• Gastrointestinal Neoplasms/diagnosis
• Gastrointestinal Neoplasms/genetics
• Humans
• Liver Neoplasms/genetics
• RNA, Circular/analysis
• RNA, Circular/genetics

• 91772279 National Natural Science Foundation of China
• 201811646025 National Undergraduate Training Program for Innovation and Entrepreneurship
• 2017SRIP1918 Student Research and Innovation Program of Ningbo University
• 2018SRIP2507 Student Research and Innovation Program of Ningbo University
• 2019SRIP1902 Student Research and Innovation Program of Ningbo University
• 2017C110019 Scientific Innovation Team Project of Ningbo
• K. C. Wong Magna Found in Ningbo University

• Early gastric cancer
• biomarker
• circular RNA
• clinical significance
• hsa_circ_0005654

• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Female
• Humans
• Male
• Middle Aged
• RNA, Circular/genetics
• RNA, Circular/metabolism
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism

• 2016009 Key Subjects of Ningbo No.2 Hospital

This study aimed to investigate the clinical significance of circular RNA 0016788 (circ_0016788) regarding its correlation with tumor progression and survival in hepatocellular carcinoma (HCC).

Two hundred and seventy‐eight HCC patients who received tumor resection were retrospectively analyzed. Circ_0016788 expression in 278 tumor tissues and 116 adjacent tissues was detected by reverse transcription‐quantitative polymerase chain reaction.

Circ_0016788 was elevated in tumor tissue compared with adjacent tissue, and it had an excellent value in distinguishing tumor tissue from adjacent tissue (area under the curve: 0.913; 95% confidence interval: 0.885‐0.941). Furthermore, circ_0016788 correlated to higher performance status score, larger tumor size, increased Barcelona clinic liver cancer (BCLC) stage, abnormal aspartate aminotransferase, abnormal alpha‐fetoprotein, and abnormal carbohydrate antigen 199 levels. Moreover, by Kaplan‐Meier curve and log‐rank test, circ_0016788 high expression correlated with shorter overall survival (OS). Importantly, multivariate Cox's regression analysis displayed that circ_0016788 high expression, older age (≥60 years), history of hepatitis B, history of liver cirrhosis, raised Child‐Pugh stage (B vs A), multifocal disease, largest tumor size (≥5 cm), and increased BCLC stage (B vs A) were independent predictors for poorer OS.

Circ_0016788 displays the potential as a biomarker for assisting personalized treatment, tumor management, and prognosis surveillance in surgical HCC patients.

• biomarker
• circular RNA 0 016 788
• hepatocellular carcinoma
• overall survival
• progression

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumour, which has posed a heavy health and financial burden worldwide. Due to limited symptoms at the early stage and the limitation in current biomarkers, HCC patients are usually diagnosed at the advanced stage with a pessimistic overall survival rate. Circular RNAs (circRNAs) are a subclass of single‐stranded RNAs characterized by a covalently closed loop structure without 3’‐ or 5’‐end. With advances in high‐throughput sequencing technology and bioinformatics, accumulating studies have demonstrated the promotor or suppressor roles of circRNAs in the carcinogenesis, progression, and metastasis of HCC. Moreover, circRNAs are characteristic of higher abundance, stability and conservation compared with linear RNAs. Therefore, circRNAs have emerged as one of the most promising diagnostic and prognostic biomarkers for HCC with reliable accuracy, sensitivity and specificity. In this review, we briefly introduce the characteristics of circRNAs and summarize the roles of circRNAs in the biological procedures of HCC. Furthermore, we provide an overview on the potential diagnostic and prognostic value of circRNAs as biomarkers for patients with HCC. Finally, we discuss future perspectives of circRNAs in cancer research.

• circular RNAs
• diagnostic biomarker
• hepatocellular carcinoma
• prognostic biomarker

Circular RNA (circRNA) plays an important role in the development of diseases, and it provides a novel idea for drug development. Accurate identification of circRNAs is important for a deeper understanding of their functions. In this study, we developed a new classifier, CirRNAPL, which extracts the features of nucleic acid composition and structure of the circRNA sequence and optimizes the extreme learning machine based on the particle swarm optimization algorithm. We compared CirRNAPL with existing methods, including blast, on three datasets and found CirRNAPL significantly improved the identification accuracy for the three datasets, with accuracies of 0.815, 0.802, and 0.782, respectively. Additionally, we performed sequence alignment on 564 sequences of the independent detection set of the third data set and analyzed the expression level of circRNAs. Results showed the expression level of the sequence is positively correlated with the abundance. A user-friendly CirRNAPL web server is freely available at http://server.malab.cn/CirRNAPL/.

• ACC, Accuracy
• CNN, Convolutional Neural Networks
• Circular RNA
• DAC, Dinucleotide-based auto-covariance
• DACC, Dinucleotide-based auto-cross-covariance
• DCC, Dinucleotide-based cross-covariance
• ELM, extreme learning machine
• Expression level
• Extreme learning machine
• GAC, Geary autocorrelation
• Identification
• MAC, Moran autocorrelation
• MCC, Matthews Correlation Coefficient
• MRMD, Maximum-Relevance-Maximum-Distance
• NMBAC, Normalized Moreau–Broto autocorrelation
• PC-PseDNC-General, General parallel correlation pseudo-dinucleotide composition
• PCGs, protein coding genes
• PSO, particle swarm optimization algorithm
• Particle swarm optimization algorithm
• PseDPC, Pseudo-distance structure status pair composition
• PseSSC, Pseudo-structure status composition
• RBF, radial basis function
• RF, random forest
• SC-PseDNC-General, General series correlation pseudo-dinucleotide composition
• SE, Sensitivity
• SP, Specifity
• SVM, support vector machine
• Triplet, Local structure-sequence triplet element
• circRNA, circular RNA
• lncRNAs, long non-coding RNAs

• Biomarkers
• Circular RNAs
• Gastrointestinal cancers
• Prognostic indicator
• Signaling pathways
• microRNA sponge

• Biomarkers
• Epigenesis, Genetic
• Gastrointestinal Neoplasms/genetics
• Gastrointestinal Neoplasms/pathology
• Humans
• MicroRNAs/genetics
• Prognosis
• RNA Splicing
• RNA, Circular

• R01 AI050875 NIAID NIH HHS
• R21 AI121700 NIAID NIH HHS

This present study aimed to investigate the correlation of circular RNA SMARCA5 (circ‐SMARCA5) with clinicopathological features and overall survival (OS), and the effect of circ‐SMARCA5 on cell proliferation and chemotherapy sensitivity to cisplatin/gemcitabine in intrahepatic cholangiocarcinoma (ICC).

Totally 92 primary ICC patients who underwent resection were recruited, and their tumor tissues and adjacent tissues were collected for circ‐SMARCA5 detection. The effect of circ‐SMARCA5 on cell proliferation and chemotherapy sensitivity was detected after circ‐SMARCA5 overexpression plasmid transfection into TFK‐1 and HuH‐28 ICC cells.

Circ‐SMARCA5 expression was reduced in ICC tumor tissues compared to adjacent tissues. Tumor circ‐SMARCA5 high expression was negatively associated with Eastern Cooperative Oncology Group performance score, T stage, N stage, TNM stage, and abnormal CA199 status. Furthermore, OS was increased in patients with tumor circ‐SMARCA5 high expression compared with those with low expression, and further multivariate Cox's regression demonstrated that tumor circ‐SMARCA5 high expression was an independent predictive factor for longer OS. In TFK‐1 and HuH‐28 ICC cells, circ‐SMARCA5 upregulation decreased cell proliferation, reduced relative cell viability in cisplatin‐treated as well as gemcitabine‐treated cells, and also decreased inhibitory concentration by 50% value (IC₅₀) of cisplatin and gemcitabine.

The correlation of circ‐SMARCA5 with favorable clinical tumor features, survival profile, and its promoting effect on chemotherapy sensitivity implies its potential as a valuable biomarker in monitoring disease progression and prognosis of ICC.

• cell proliferation
• chemotherapy sensitivity
• circular RNA SMARCA5
• intrahepatic cholangiocarcinoma
• prognosis

• clinical significance
• diagnostics
• gastric cancer
• hsa_circ_0067582
• qRT-PCR

• ICD
• LTX-401
• antitumor agent
• hepatocellular carcinoma
• immunotherapy
• oncolytic compound

• RT-qPCR
• biomarkers
• circRNAs
• diagnosis
• gene expression

Circular RNAs (circRNAs) play important roles in the progression of cancers, but the precise role of circRNAs in the diagnosis and prognosis of hepatocellular carcinoma (HCC) remains to be clarified. The aim of the current study was to explore the diagnostic and prognostic values of hsa_circ_0003998 in HCC.

CircRNAs expression was measured using RNA-seq analysis from HCC tissues (n=6) (three cases with or without portal vein invasion). Hsa_circ_0003998 in 200 pairs of HCC and adjacent noncancerous tissues and HCC cell lines was examined using qRT-PCR and the clinicopathologic significance was determined. We also detected the plasma levels of hsa_circ_0003998 in HCC, hepatitis B patients and healthy controls. The clinical diagnosis and prognostic values were further determined using receiver operating characteristic (ROC) curve, Kaplan–Meier curve and Cox regression.

Hsa_circ_0003998 was upregulated in HCC tissues (P<0.001) and HCC cell lines (HepG2, HuH7, MHCC97H) (P<0.001). In addition, upregulation of hsa_circ_0003998 level was associated with higher serum alpha-fetoprotien (AFP) level (P=0.003), larger tumor diameter (P=0.009), lower differentiation level (P=0.023) and microvascular invasion (P=0.028). The plasma level of hsa_circ_0003998 in HCC patients was significantly higher than those in hepatitis B patients (P<0.001) and healthy controls (P<0.001). Its level was significantly reduced after the operation (P<0.001). The area under the ROC curve (AUC) for distinguishing HCC from adjacent noncancerous tissues was 0.894 (95% CI=0.86–0.922, P<0.001), the sensitivity and specificity were 0.84 and 0.8, respectively. Comparing with hepatitis B patients and healthy controls, hsa_circ_0003998, respectively, had an AUC value of 0.833 (95% CI=0.763–0.889, P<0.001) and 0.892 (95% CI=0.831–0.937, P<0.001). Their sensitivity and specificity were 0.83, 0.7 and 0.8, 0.84, respectively. Moreover, the combination of hsa_circ_0003998 and AFP showed the highest AUC value of 0.947, the sensitivity and specificity were 0.88 and 0.92, respectively. The hsa_circ_0003998 (P=0.003) and AFP (P=0.008) levels were independent prognostic factors for HCC. The overall survival of HCC patients with high level of hsa_circ_0003998 was significantly poorer than those with low level (P=0.005).

Our findings suggest that hsa_circ_0003998 may be used as a novel potential biomarker for the diagnosis and prognosis of HCC patients.

• biomarker
• circular RNA
• diagnosis
• hepatocellular carcinoma
• hsa_circ_0003998
• prognosis

• Circular RNA
• Diagnostic biomarker
• Hepatocellular carcinoma
• Prognostic biomarker
• Therapeutic target
• miRNA sponge

• CircRNA
• biomarker
• cancer
• diagnosis

• Area Under Curve
• Biomarkers, Tumor/genetics
• Humans
• Likelihood Functions
• Neoplasms/diagnosis
• Neoplasms/genetics
• Odds Ratio
• RNA, Circular/analysis
• RNA, Circular/genetics
• Sensitivity and Specificity

• Biomarkers
• Liquid biopsies
• Non-coding RNA
• circRNA

• HCC
• circRNA
• diagnostic biomarker
• miRNA sponge
• therapeutic target

• biomarker
• circular RNA
• gene expression
• hepatocellular carcinoma
• metastasis