Diagnostic Accuracy of Circular RNAs in Different Types of Samples for Detecting Hepatocellular Carcinoma: A Meta-Analysis

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.

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Accuracy of Various Forms of Contrast-Enhanced MRI for Diagnosing Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.680691 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chun Zhao ◽

Hongyan Dai ◽

Juwei Shao ◽

Qian He ◽

Wei Su ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Sensitivity And Specificity ◽

Meta Analysis ◽

High Sensitivity ◽

Cochrane Library ◽

Significant Heterogeneity ◽

Chi Square ◽

Enhanced Mri ◽

Contrast Enhanced ◽

Contrast Enhanced Mri

BackgroundContrast-enhanced MRI can be used to identify patients with hepatocellular carcinoma (HCC). However, studies around the world have found differing diagnostic accuracies for the technique. Hence, we designed this meta-analysis to assess the accuracy of contrast-enhanced MRI for HCC diagnosis.MethodsWe conducted a systematic search for all studies reporting the diagnostic accuracy of contrast-enhanced MRI for HCC in the databases of MEDLINE, EMBASE, Cochrane Library, Web of Science, SCOPUS, ScienceDirect, and Google Scholar from inception until January 2021. We used the “Midas” package from the STATA software to perform the meta-analysis.ResultsOur study was based on 21 publications with 5,361 patients. The pooled HCC diagnosis sensitivity and specificity were 75% (95% CI, 70%–80%) and 90% (95% CI, 88%–92%), respectively, for gadoxetic acid-enhanced MRI; and they were 70% (95% CI, 57%–81%) and 94% (95% CI, 85%–97%), respectively, for MRI with extracellular contrast agents (ECA-MRI). We found significant heterogeneity with a significant chi-square test and an I2 statistic >75%. We also found significant publication bias as per Deeks’ test results and funnel plot.ConclusionWe found that both types of contrast-enhanced MRI are accurate diagnostic and surveillance tools for HCC and offer high sensitivity and specificity. Further studies on different ethnic populations are required to strengthen our findings.

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Diagnostic Accuracy of Serum/Plasma Circular RNAs and the Combination of Circular RNAs and α-Fetoprotein for Detecting Hepatocellular Carcinoma: A Meta-Analysis

Frontiers in Genetics ◽

10.3389/fgene.2021.722208 ◽

2021 ◽

Vol 12 ◽

Author(s):

Guilin Nie ◽

Dingzhong Peng ◽

Bei Li ◽

Jiong Lu ◽

Yulong Cai ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Diagnostic Accuracy ◽

Likelihood Ratio ◽

Meta Analysis ◽

Genomic Medicine ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Cochrane Library ◽

Circular Rnas ◽

Liquid Biopsies

The lack of an accurate biomarker in hepatocellular carcinoma (HCC) has hindered early detection, diagnosis, and treatment. Circular RNAs (circRNAs), which can be used as novel biomarkers in liquid biopsies, have been brought to light as a result of the advances in research on molecular biomarkers and the progression of genomic medicine. We conducted a meta-analysis of the diagnostic accuracy of serum/plasma circRNAs or the combination of circRNAs and α-fetoprotein (AFP) in HCC. We identified eight studies that met the inclusion/exclusion criteria from PubMed, Web of Science, EMBASE, and Cochrane Library databases. The data were pooled, and the sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) with 95% confidence intervals (CIs) were calculated. The areas under the summary receiver operator characteristic (SROC) curves (AUCs) were also calculated. The sensitivity of circRNAs was 0.82 (95% CI: 0.78–0.85), and the specificity was 0.82 (95% CI: 0.78–0.86). The sensitivity of AFP was 0.65 (95% CI: 0.61–0.68), and the specificity was 0.90 (95% CI: 0.85–0.93). The AUC was 0.89 (95% CI: 0.86–0.91) for circRNAs and 0.77 (95% CI: 0.74–0.81) for AFP. The sensitivity of the combination of circRNAs and AFP was 0.88 (95% CI: 0.84–0.92), specificity was 0.86 (95% CI: 0.80–0.91), and AUC was 0.94 (95% CI: 0.91–0.96). Additionally, a subgroup analysis was conducted based on the control groups used; the diagnostic accuracy was particularly high in the comparison of HCC vs. healthy controls. In summary, serum/plasma circRNAs are accurate biomarkers suitable for clinical use for detecting HCC, and the combination of circRNAs and AFP improved the diagnostic accuracy.

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The effects of several postoperative adjuvant therapies for hepatocellular carcinoma patients with microvascular invasion after curative resection: a systematic review and meta-analysis

Cancer Cell International ◽

10.1186/s12935-021-01790-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jiarui Yang ◽

Hao Liang ◽

Kunpeng Hu ◽

Zhiyong Xiong ◽

Mingbo Cao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Conservative Treatment ◽

Curative Resection ◽

Postoperative Radiotherapy ◽

Meta Analysis ◽

Microvascular Invasion ◽

Cochrane Library ◽

Conservative Group ◽

Adjuvant Therapies ◽

Significant Difference

Abstract Background For patients with hepatocellular carcinoma (HCC) with microvascular invasion (MVI) after curative resection, the effects of various postoperative adjuvant therapies are not summarized in detail, and the comparison between the effects of various adjuvant therapies is still unclear. Thus, we collected existing studies on postoperative adjuvant therapies for patients with HCC with MVI after curative resection and analyzed the effects of various adjuvant therapies. Method We collected all studies on postoperative adjuvant therapy for patients with HCC with MVI after curative resection from PubMed, EMBASE, Cochrane Library and SinoMed ending on May 1, 2019. Overall survival (OS) and disease-free/recurrence-free survival (RFS) between each group were compared in these studies by calculating the pooled hazard ratio (HR) and 95% confidence interval (CI). All statistical analyses were assessed by two authors independently. Result A total of 13 studies were included in this study, including 824 postoperative adjuvant transarterial chemoembolization (pa-TACE) patients, 90 postoperative radiotherapy patients, 57 radiofrequency ablation (RFA)/re-resection patients, 16 sorafenib patients and 886 postoperative conservative treatment patients. The results showed that pa-TACE significantly improved OS and RFS compared with postoperative conservative treatment in patients with HCC with MVI after curative resection (HR: 0.64, 95% CI: 0.55–0.74, p < 0.001; HR: 0.70, 95% CI: 0.62–0.78, p < 0.001, respectively). There was no significant difference in OS between pa-TACE and radiotherapy in patients with HCC with MVI (HR: 1.75, 95% CI: 0.92–3.32, p = 0.087). RFS in patients with HCC with MVI after pa-TACE was worse than that after postoperative adjuvant radiotherapy (HR: 2.29, 95% CI: 1.43–3.65, p < 0.001). The prognosis of pa-TACE and RFA/re-resection in patients with MVI with recurrent HCC had no significant differences (HR: 0.65, 95% CI: 0.09–4.89, p = 0.671). Adjuvant treatments significantly improved the OS and RFS of patients compared with the postoperative conservative group (HR: 0.580, 95% CI: 0.480–0.710, p < 0.001; HR: 0.630, 95% CI: 0.540–0.740, p < 0.001, respectively). Conclusion Compared with postoperative conservative treatment, pa-TACE, postoperative radiotherapy and sorafenib can improve the prognosis of patients with hepatocellular carcinoma with microvascular invasion after curative resection. Postoperative radiotherapy can reduce the recurrence of patients with HCC with MVI after curative resection compared with pa-TACE.

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Adjuvant Transarterial Chemoembolization Following Curative-Intent Hepatectomy Versus Hepatectomy Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Cancers ◽

10.3390/cancers13122984 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2984

Author(s):

Stepan M. Esagian ◽

Christos D. Kakos ◽

Emmanouil Giorgakis ◽

Lyle Burdine ◽

J. Camilo Barreto ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Randomized Controlled Trials ◽

Transarterial Chemoembolization ◽

Meta Analysis ◽

Risk Of Bias ◽

Cochrane Library ◽

Controlled Trials ◽

Curative Intent ◽

Randomized Controlled

The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.

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Does the Intradiscal Injection of Platelet Rich Plasma Have Any Beneficial Role in the Management of Lumbar Disc Disease?

Global Spine Journal ◽

10.1177/2192568221998367 ◽

2021 ◽

pp. 219256822199836

Author(s):

Sathish Muthu ◽

Madhan Jeyaraman ◽

Girinivasan Chellamuthu ◽

Naveen Jeyaraman ◽

Rashmi Jain ◽

...

Keyword(s):

Beneficial Effect ◽

Platelet Rich Plasma ◽

Lumbar Disc ◽

Meta Analysis ◽

Cochrane Library ◽

Significant Heterogeneity ◽

Disc Disease ◽

Lumbar Disc Disease ◽

Beneficial Role ◽

Sf 36

Study Design: Systematic review and meta-analysis. Objectives: We performed this meta-analysis to evaluate whether intradiscal Platelet Rich Plasma(PRP) injection has any beneficial role in the management of lumbar disc disease. Methods: We conducted independent and duplicate electronic database searches including PubMed, Embase, and Cochrane Library till September 2020 for studies investigating the role of intradiscal PRP in the management of lumbar disc disease. The analysis was performed in the R platform using OpenMeta[Analyst] software. Results: 13 studies including 2 RCTs, 5 prospective, and 6 retrospective studies involving 319 patients were included in the meta-analysis. A single-arm meta-analysis of the included studies showed a beneficial effect of the intervention in terms of pain relief outcomes like VAS score (p < 0.001), pain component of SF-36 (p = 0.003) while such improvement was not seen in functional outcome measures like ODI score (p = 0.071), the physical component of SF-36 (p = 0.130) with significant heterogeneity noted among the included studies. No structural improvement in magnetic resonance imaging was observed (p = 0.106). No additional procedure-related adverse events were noted in the included studies (p = 0.662). Conclusion: There is a paucity of high-quality studies to give conclusive evidence on the benefits of intradiscal PRP for lumbar disc disease. Although intradiscal PRP injection has shown some beneficial effect in controlling pain for lumbar disc disease, we could not find structural or functional improvement from the included studies. Hence, we recommend large double-blind double-arm randomized controlled studies to analyze the benefits of the intervention being analyzed.

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Individual or combined transcatheter arterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma: a time-to-event meta-analysis

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02188-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Chuang Jiang ◽

Gong Cheng ◽

Mingheng Liao ◽

Jiwei Huang

Keyword(s):

Hepatocellular Carcinoma ◽

Radiofrequency Ablation ◽

Transcatheter Arterial Chemoembolization ◽

Meta Analysis ◽

Combined Treatment ◽

Similar Rate ◽

Cochrane Library ◽

China National Knowledge Infrastructure ◽

Knowledge Infrastructure ◽

Arterial Chemoembolization

Abstract Background There is still some debate as to whether transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA) is better than TACE or RFA alone. This meta-analysis aimed to compare the efficacy and safety of TACE plus RFA for hepatocellular carcinoma (HCC) with RFA or TACE alone. Methods We searched PubMed, MEDLINE, Embase, Cochrane Library, and CNKI (China National Knowledge Infrastructure) for all relevant randomized controlled trials and retrospective studies reporting overall survival (OS), recurrence-free survival (RFS), and complications of TACE plus RFA for HCC, compared with RFA or TACE alone. Results Twenty-one studies involving 3413 patients were included. TACE combined with RFA was associated with better OS (hazard ratio [HR]=0.62, 95% confidence intervals [CI] = 0.55–0.71, P < 0.001) and RFS (HR = 0.52, 95% CI = 0.39–0.69, P < 0.001) than TACE alone; compared with RFA alone, TACE plus RFA resulted in longer OS (HR = 0.63, 95% CI = 0.53–0.75, P < 0.001) and RFS (HR = 0.60, 95% CI = 0.51–0.71, P < 0.001). Subgroup analyses by tumor size also showed that combined treatment resulted in better OS and RFS compared with RFA alone in patients with HCC larger than 3 cm. Combined treatment resulted in similar rate of major complications compared with TACE or RFA alone (OR = 1.78, 95% CI = 0.99–3.20, P = 0.05; OR = 1.00, 95% CI = 0.42–2.38, P = 1.00, respectively). Conclusions TACE combined with RFA was more effective for HCC than TACE alone. For patients with a tumor larger than 3 cm, the combined treatment also achieved a better effect than RFA alone.

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Prevalence of depression and depressive symptoms among outpatients: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2017-017173 ◽

2017 ◽

Vol 7 (8) ◽

pp. e017173 ◽

Cited By ~ 83

Author(s):

Jinghui Wang ◽

Xiaohang Wu ◽

Weiyi Lai ◽

Erping Long ◽

Xiayin Zhang ◽

...

Keyword(s):

Systematic Review ◽

Depressive Symptoms ◽

Meta Analysis ◽

Significant Proportion ◽

Depression Scale ◽

Developed Countries ◽

Self Report ◽

Cochrane Library ◽

Significant Heterogeneity ◽

Prevalence Of Depression

ObjectivesDepression and depressive symptoms are common mental disorders that have a considerable effect on patients’ health-related quality of life and satisfaction with medical care, but the prevalence of these conditions varies substantially between published studies. The aim of this study is to conduct a systematic review and meta-analysis to provide a precise estimate of the prevalence of depression or depressive symptoms among outpatients in different clinical specialties.DesignSystematic review and meta-analysis.Data sources and eligibility criteriaThe PubMed and PsycINFO, EMBASE and Cochrane Library databases were searched to identify observational studies that contained information on the prevalence of depression and depressive symptoms in outpatients. All studies included were published before January 2016. Data characteristics were extracted independently by two investigators. The point prevalence of depression or depressive symptoms was measured using validated self-report questionnaires or structured interviews. Assessments were pooled using a random-effects model. Differences in study-level characteristics were estimated by meta-regression analysis. Heterogeneity was assessed using standard χ2tests and the I2statistic. The study protocol has been registered with PROSPERO under number CRD42017054738.ResultsEighty-three cross-sectional studies involving 41 344 individuals were included in this study. The overall pooled prevalence of depression or depressive symptoms was 27.0% (10 943/41 344 individuals; 95% CI 24.0% to 29.0%), with significant heterogeneity between studies (p<0.0001, τ2=0.3742, I2=96.7%). Notably, a significantly higher prevalence of depression and depressive symptoms was observed in outpatients than in the healthy controls (OR 3.16, 95% CI 2.66 to 3.76, I2=72.0%, χ2=25.33). The highest depression/depressive symptom prevalence estimates occurred in studies of outpatients from otolaryngology clinics (53.0%), followed by dermatology clinics (39.0%) and neurology clinics (35.0%). Subgroup analyses showed that the prevalence of depression and depressive symptoms in different specialties varied from 17.0% to 53.0%. The prevalence of depression and depressive symptoms was higher among outpatients in developing countries than in outpatients from developed countries. Moreover, the prevalence of depression and depressive symptoms in outpatients slightly decreased from 1996 to 2010. Regarding screening instruments, the Beck Depression Inventory led to a higher estimate of the prevalence of depression and depressive symptoms (1316/4702, 36.0%, 95% CI 29.0% to 44.0%, I2=94.8%) than the Hospital Anxiety and Depression Scale (1003/2025, 22.0%, 95% CI 12.0% to 35.0%, I2=96.6%).ConclusionOur study provides evidence that a significant proportion of outpatients experience depression or depressive symptoms, highlighting the importance of developing effective management strategies for the early identification and treatment of these conditions among outpatients in clinical practice. The substantial heterogeneity between studies was not fully explained by the variables examined.

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Clinical and Molecular Characteristics Associated with Survival in Advanced Melanoma Treated with Checkpoint Inhibitors

Journal of Oncology ◽

10.1155/2018/6279871 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Sunil Badami ◽

Sunil Upadhaya ◽

Ravi Kanth Velagapudi ◽

Pushyami Mikkilineni ◽

Ranju Kunwor ◽

...

Keyword(s):

Clinical Trials ◽

Randomized Clinical Trials ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Random Effect ◽

Eastern Cooperative Oncology Group ◽

Advanced Melanoma ◽

Cochrane Library ◽

Molecular Characteristics ◽

Significant Heterogeneity

Background. We performed meta-analysis to gather more evidence regarding clinical-molecular subgroups associated with better overall survival (OS) in advanced melanoma treated with checkpoint inhibitors. Materials and Methods. We performed a systematic search of PubMed, Scopus, Cochrane Library, and clinical trial.gov. Randomized clinical trials that compared a checkpoint inhibitor (nivolumab or pembrolizumab) with investigator choice chemotherapy or ipilimumab were included in our study. Hazard ratios (HR) and confidence interval (CI) were calculated for progression-free survival (PFS) and OS for each subgroup using generic inverse model along with the random effect method. Results. A total of 6 clinical trials were eligible for the meta-analysis. OS was prolonged in wild BRAF subgroup (HR 0.65, 95% CI 0.49-0.85, p 0.002), Programmed cell death subgroup (PD-1+) (HR 0.57, 95% CI 0.41-0.80, p 0.001), and high lactate dehydrogenase (LDH) level subgroup (HR 0.60, 95% CI 0.38-0.95, p 0.03). Similarly, we found increased OS in eastern cooperative oncology group (ECOG) 1, males and age >65 years subgroups. Conclusions. Checkpoint inhibitors significantly increased OS in patients with wild BRAF, positive PD-1, and high LDH. However, results should be interpreted keeping in mind associated significant heterogeneity. The results of this study should help in designing future clinical trials.

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Serum Cytokines in Erythema Nodosum Leprosum Versus Non-Reactional Leprosy: A Systematic Review and Meta-analysis

Acta Medica Philippina ◽

10.47895/amp.v53i2.169 ◽

2019 ◽

Vol 53 (2) ◽

Author(s):

Mia Katrina R. Gervasio ◽

Felix Paolo J. Lizarondo ◽

Belen L. Dofitas

Keyword(s):

Erythema Nodosum ◽

Meta Analysis ◽

Underlying Mechanism ◽

Cochrane Library ◽

Significant Heterogeneity ◽

Sample Sizes ◽

Cross Sectional ◽

Erythema Nodosum Leprosum ◽

Keywords Cytokines ◽

Newcastle Ottawa Scale

Background. Erythema nodosum leprosum is an immune-mediated complication of leprosy whose underlying mechanism has not yet been fully elucidated, making management difficult.Objectives. To determine the serum cytokine profile of ENL compared to non-reactional leprosy states. Methods. An open literature search was performed using MEDLINE, Cochrane Library, TRIP and HERDIN electronic databases using the keywords ("cytokines" or “inflammatory mediators”) and (“erythema nodosum leprosum” or “ENL”) and (“leprosy” or “lepra”). Studies were selected by two independent review authors. Risk of bias was assessed using the Newcastle-Ottawa Scale and statistical analysis was performed using RevMan 5.3 software. Results. Eight cross-sectional studies with 197 participants were included. Meta-analysis showed that both serum IL-17 and serum IFN-γ were significantly decreased (Z 2.39, p = 0.02 and Z 2.74, p = 0.01, respectively) in ENL compared to non-reactional states. However, for IL-1β, IL-6, IL-10, IL-22, TNF-α and TGF-β, no significant differences were found between the two groups. Conlusion. ENL appears to be an exacerbation of the Th2 cytokine response seen in the lepromatous pole of leprosy. However, despite pooling of data, sample sizes remain small resulting in significant heterogeneity. Future studies involving large sample sizes and investigating a wider range of cytokines are encouraged.

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Systematic Review and Meta-Analysis of the Utility of Circular RNAs as Biomarkers of Hepatocellular Carcinoma

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2019/1684039 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Qingqin Hao ◽

Yadi Han ◽

Wei Xia ◽

Qinghui Wang ◽

Huizhong Qian

Keyword(s):

Likelihood Ratio ◽

Meta Analysis ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Diagnostic Odds Ratio ◽

Clinicopathological Characteristics ◽

Cochrane Library ◽

Circular Rnas ◽

Clinical Value ◽

Sensitivity Specificity

Emerging studies have reported circRNAs were dysregulated in HCC. However, the clinical value of these circRNAs remains to be clarified. Herein, we aimed to comprehensively explore their association with the diagnosis, prognosis, and clinicopathological characteristics of HCC. PubMed, EMBASE, Web of Science, and Cochrane Library databases were comprehensively searched for eligible studies up to October 30, 2018. The diagnostic effect was evaluated by the pooled sensitivity, specificity, and other indexes. The pooled hazard ratio (HR) for overall survival (OS) and recurrence free survival (RFS) was calculated to assess the prognostic value. Ten studies on diagnosis, 12 on prognosis, and 23 on clinicopathology were identified from the databases. A total of 11 upregulated and 11 downregulated circRNAs showed an association with clinicopathological features of HCC. For the diagnosis analyses, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of circRNAs for HCC were 0.74 (95%CI: 0.65-0.82) and 0.76 (95%CI: 0.70-0.81), 3.1 (95%CI: 2.5-3.8), 0.34 (95%CI: 0.25-0.47), and 9 (95%CI: 6-14), respectively. The area under SROC curve (AUC) was 0.81 (95% CI: 0.78–0.84), indicating moderate diagnostic accuracy. In stratified analyses, the diagnostic performance of circRNAs varied based on the source of control and specimen type. For the prognosis analyses, increased expression of upregulated circRNAs was associated with worse OS (HR: 3.67, 95%: 2.07-6.48), while high expression of downregulated circRNAs was associated with better OS (HR: 0.38, 95%: 0.30-0.48). In conclusion, this study reveals that circRNAs may serve as promising diagnostic and prognostic biomarkers for HCC. However, further investigations are still required to explore the clinical value of circRNAs.

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