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The expression of circRNAs as a promising biomarker in the diagnosis and prognosis of human cancers: a systematic review and meta-analysis.

ABSTRACT: CircRNAs, a type of non-coding RNAs with special loop structure, of which the aberrant expression is closely related to tumor growth, proliferation, metastasis and recurrence. It remains unclear whether they have the potential to be biomarkers for diagnosis and prognosis of cancers. The study aims to clarify the relationship of circRNAs expression with cancers diagnosis and prognosis.Sensitivity, specificity, area under curve (AUC) and receiver operating characteristic curve (ROC) were calculated to evaluate the diagnostic efficacy; Hazard ratio (HR) of overall survival (OS), disease free survival (DFS) and recurrence free survival (RFS) were calculated to evaluate the association between circRNAs expression and survival of cancer patients.A total of 27 studies were involved in the meta-analysis, including 16 diagnostic and 11 prognostic articles. Among the diagnostic studies, 18 kinds of circRNAs had been investigated, in which 3 were up regulated and 15 were down regulated. Their pooled sensitivity, specificity and AUC were 0.71(0.65-0.77), 0.77(0.72-0.81) and 0.81(0.77-0.84), respectively. In stratified analysis, a higher specificity was shown in circRNAs for diagnosing gastric cancer and hepatocellular cancer. 12 circRNAs were involved in the prognostic studies, including 6 up-regulated and 6 down-regulated circRNAs. Their overall HR of OS and DFS/RFS were 1.37(0.98-1.75) and 2.28 (0.77-3.79), respectively.CircRNAs have the potential to be biomarkers for diagnosis and prognosis of cancers. Further investigations are still needed to explore the clinical value of circRNAs as tumor markers.

SUBMITTER: Ding HX

PROVIDER: S-EPMC5837763 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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CircRNAs as promising biomarker in diagnosis of breast cancer: An updated meta-analysis.

Project description:BackgroundCircular RNAs (circRNAs) have been identified to be involved in onset and progression of multiple malignant tumors. The present study aimed to systematically evaluate the diagnostic values of circRNAs in breast cancer.MethodsThe PubMed, Web of Science, Embase, CNKI, and Wanfang online databases were searched for the relevant studies before December 31, 2020. Statistical analysis of the diagnostic tests was performed based on STATA 16.0, Meta-DiSc 1.4, and RevMan 5.3 software. The threshold effect and publication bias were measured by the Spearman correlation and Deeks' funnel plot asymmetry test, respectively.ResultsTwenty-one studies from 13 articles were included in this meta-analysis. The pooled sensitivity and specificity were 0.77 and 0.71, respectively. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and overall diagnostic odds ratio (DOR) were 2.6, 0.33, and 8, respectively. Furthermore, the area under the summary receiver operator characteristic curve was 0.80. In addition, down-regulated circRNAs achieved a diagnostic performance higher than up-regulated circRNAs, with area under curve (AUC) values of 0.81 and 0.74, respectively. Studies based on tissue samples presented better diagnostic accuracy than those based on plasma samples, with AUC values of 0.80 and 0.67. In addition, two circRNAs, including circ_0001073 and circTADA2A-E5/E6, showed higher diagnostic values, with AUC value of 0.990 and 0.937, respectively. According to the results of meta-regression, the case size (p<0.05) might be the source of the heterogeneity.ConclusionCircRNAs exhibited a high diagnostic value for breast cancer and may function as potential diagnostic biomarkers for breast cancer.

| S-EPMC8418489 | biostudies-literature

The clinical role of microRNA-21 as a promising biomarker in the diagnosis and prognosis of colorectal cancer: a systematic review and meta-analysis.

Project description:This systematic analysis aimed to investigate the value of microRNA-21 (miR-21) in colorectal cancer for multiple purposes, including diagnosis and prognosis, as well as its predictive power in combination biomarkers. Fifty-seven eligible studies were included in our meta-analysis, including 25 studies for diagnostic meta-analysis and 32 for prognostic meta-analysis. For the diagnostic meta-analysis of miR-21 alone, the overall pooled results for sensitivity, specificity, and area under the curve (AUC) were 0.64 (95% CI: 0.53-0.74), 0.85 (0.79-0.90), and 0.85 (0.81-0.87), respectively. Circulating samples presented corresponding values of 0.72 (0.63-0.79), 0.84 (0.78-0.89), and 0.86 (0.83-0.89), respectively. For the diagnostic meta-analysis of miR-21-related combination biomarkers, the above three parameters were 0.79 (0.69-0.86), 0.79 (0.68-0.87), and 0.86 (0.83-0.89), respectively. Notably, subgroup analysis suggested that miRNA combination markers in circulation exhibited high predictive power, with sensitivity of 0.85 (0.70-0.93), specificity of 0.86 (0.77-0.92), and AUC of 0.92 (0.89-0.94). For the prognostic meta-analysis, patients with higher expression of miR-21 had significant shorter disease-free survival [DFS; pooled hazard ratio (HR): 1.60; 95% CI: 1.20-2.15] and overall survival (OS; 1.54; 1.27-1.86). The combined HR in tissues for DFS and OS were 1.76 (1.31-2.36) and 1.58 (1.30-1.93), respectively. Our comprehensive systematic review revealed that circulating miR-21 may be suitable as a diagnostic biomarker, while tissue miR-21 could be a prognostic marker for colorectal cancer. In addition, miRNA combination biomarkers may provide a new approach for clinical application.

| S-EPMC5546529 | biostudies-literature

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| S-EPMC8422728 | biostudies-literature

miR-203 as a novel biomarker for the diagnosis and prognosis of colorectal cancer: a systematic review and meta-analysis.

Project description:We sought to systematically evaluate the diagnostic and prognostic value of miR-203 in patients with colorectal cancer. To explore the diagnostic performance of miR-203, eligible studies were identified from biomedical databases. Based on these results, 11 studies were pooled and included in this meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratios of miR-203 were 0.83 (95% confidence interval, CI: 0.78-0.86), 0.80 (95% CI: 0.77-0.83), and 19.27 (95% CI: 7.23-51.36) for the diagnosis of colorectal cancer. The area under the curve for miR-203 for diagnosing colorectal cancer was 0.89. Patients with higher expression of tissue miR-203 had poor overall survival (pooled hazard ratio: 1.63; 95% CI: 1.03-2.57, P=0.04), but serum miR-203 was not predictive (pooled hazard ratio: 1.59; 95% CI: 0.31-8.12, P=0.58). The miR-203 values of tissue and serum merged together may perhaps predict superior overall survival (pooled hazard ratio: 1.62; 95% CI: 0.93-2.82), but the effect was not significant (P=0.09).

| S-EPMC5533489 | biostudies-literature

MiR-205 as a promising biomarker in the diagnosis and prognosis of lung cancer.

Project description:MicroRNA-205 (miR-205) was revealed as a novel diagnostic and prognostic biomarker for lung cancer, but the results in the published papers were inconsistent. This meta-analysis aimed to investigate the diagnostic and prognostic roles of miR-205 in patients with lung cancer. Totally, 16 eligible articles were included, among which 10 articles investigated the diagnostic value of miR-205, 5 articles examined its prognostic values, and 1 article studied both diagnostic and prognostic values. For the diagnostic meta-analysis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the overall area under the curve of miR-205 for patients with lung cancer were 0.88 (95% CI = 0.78 - 0.94), 0.78 (95% CI = 0.66 - 0.86), 4.00 (95% CI = 2.47 - 6.49), 0.16 (95% CI = 0.08 - 0.30), 25.86 (95% CI = 9.29 - 71.95), and 0.90 (95% CI = 0.87 - 0.92), respectively, indicating that miR-205 is a useful biomarker for diagnostic of lung cancer. The subgroup analysis further demonstrated that miR-205 had an excellent overall accuracy for detection with tissue samples compare with blood samples. For the prognostic meta-analysis, the pooled outcome of the disease-free survival and recurrence-free survival analyses revealed that increased miR-205 levels had a protective role in the prognosis of patients with lung cancer (pooled HR = 0.86, 95% CI: 0.78-0.96, z = 2.83, P = 0.005). In conclusion, miR-205 may be a promising biomarker for detection, predicting the recurrence of patients with lung cancer.

| S-EPMC5696153 | biostudies-literature

MicroRNAs (miRNAs) as biomarker(s) for prognosis and diagnosis of gastrointestinal (GI) cancers.

Project description:Gastrointestinal (GI) cancers remain one of the most common malignancies and are the second common cause of cancer deaths worldwide. The limited effectiveness of therapy for patients with advanced stage and recurrent disease is a reflection of an incomplete understanding of the molecular basis of GI carcinogenesis. Major advancements have improved our understanding of pathology and pathogenesis of GI cancers, but high mortality rates, unfavorable prognosis and lack of clinical predictive biomarkers provide an impetus to investigate new sensitive and specific diagnostic and prognostic markers for GI cancers. MicroRNAs (miRNAs) are short (19-24 nucleotides) noncoding RNA molecules that regulate gene expression at the posttranscriptional level thus playing an important role in modulating various biological processes including, but not limited to developmental processes, proliferation, apoptosis, metabolism, differentiation, epithelial-mechenchymal transition and are involved in the initiation and progression of various human cancers. Unique miRNA expression profiles have been observed in various cancer types at different stages, suggesting their potential as diagnostic and prognostic biomarkers. Due to their tumor-specific and tissue-specific expression profiles, stability, robust clinical assays for detection in serum as well as in formalin-fixed tissue samples, miRNAs have emerged as attractive candidates for diagnostic and prognostic applications. This review summarizes recent research supporting the utility of miRNAs as novel diagnostic and prognostic tools for GI cancers.

| S-EPMC4113605 | biostudies-literature

Methylation of SFRP2 gene as a promising noninvasive biomarker using feces in colorectal cancer diagnosis: a systematic meta-analysis.

Project description:Methylation of secreted frizzled-related protein genes (SFRP) associated with the Wnt signaling pathway has previously been reported. However, the diagnostic role of SFRP methylation in colorectal cancer (CRC) remains unclear. A systematic search was performed to identify eligible articles for analysis. The pooled OR showed that SFRP1, SFRP2, SFRP4 and SFRP5 methylation was significantly higher in CRC and benign mucosal lesions than in normal colonic mucosa. When CRC was compared to benign mucosal lesions, SFRP1 and SFRP2 methylation had a significantly higher OR, but methylated SFRP4 and SFRP5 had a similar OR. Moreover, the pooled sensitivity, specificity and AUC (area under the curve) of methylated SFRP2 in feces of patients with CRC vs. healthy subjects was 0.71, 0.94 and 0.94, respectively. Therefore, methylation of SFRP1 and SFRP2 may be significantly correlated with CRC. However, in a study with small sample size, methylated SFRP4 and SFRP5 were not shown to be closely associated with CRC. Additionally, detection of SFRP2 methylation in feces presents a potential noninvasive biomarker for CRC diagnosis.

| S-EPMC5034263 | biostudies-literature

Tat-Interacting Protein 30 (TIP30) Expression Serves as a New Biomarker for Tumor Prognosis: A Systematic Review and Meta-Analysis.

Project description:BackgroundTat-interacting protein 30 (TIP30) is a tumor suppressor protein that has been found to be expressed in a wide variety of tumor tissues. TIP30 is involved in the control of cell apoptosis, growth, metastasis, angiogenesis, DNA repair, and tumor cell metabolism. The methylation of the TIP30 promoter is also associated with tumor prognosis. To evaluate this topic further, we conducted a systematic meta-analysis to explore the clinicopathological and prognostic significance of TIP30 for tumor patients.MethodsWe searched PubMed and EMBASE for eligible studies. We manually searched for printed journals and relevant textbooks. Subgroup analyses were performed based on the region, manuscript quality, methods of vasculogenic mimicry identification, pathology, and number of patients.ResultsFourteen studies with 1705 patients were included in this meta-analysis. A significant association was observed between high expression of TIP30 in patients with cancer with a good overall survival (hazard ratio = 0.53, 95% confidence interval: 0.41-0.69), and good recurrence-free survival or disease free survival (hazard ratio = 0.49, 95% confidence interval: 0.37-0.66). Lack of expression of TIP30 had an association with lymph node metastasis (odds ratio = 3.90, 95% confidence interval: 2.21-6.89) and high tumor node metastasis clinical stage (odds ratio = 2.10, 95% confidence interval: 1.68-2.62). The methylation of the TIP30 promoter did not significantly influence the overall survival (hazard ratio = 0.99, 95% confidence interval: 0.88-1.13) or disease free survival (hazard ratio = 0.62, 95% confidence interval: 0.19-2.02).ConclusionsTIP30 expression is associated with a good prognosis in patients with tumors. Clinical studies with large samples are needed worldwide and standardized protocols should be adopted in the future to achieve a better understanding of the relationship between tumor prognosis and TIP30.

| S-EPMC5201241 | biostudies-literature

Metabolomics for biomarker discovery in the diagnosis, prognosis, survival and recurrence of colorectal cancer: a systematic review.

Project description:Colorectal cancer (CRC) remains an incurable disease. There are no effective noninvasive techniques that have achieved colorectal cancer (CRC) diagnosis, prognosis, survival and recurrence in clinic. To investigate colorectal cancer metabolism, we perform an electronic literature search, from 1998 to January 2016, for studies evaluating the metabolomic profile of patients with CRC regarding the diagnosis, recurrence, prognosis/survival, and systematically review the twenty-three literatures included. QUADOMICS tool was used to assess the quality of them. We highlighted the metabolism perturbations based on metabolites and pathway. Metabolites related to cellular respiration, carbohydrate, lipid, protein and nucleotide metabolism were significantly altered in CRC. Altered metabolites were also related to prognosis, survival and recurrence of CRC. This review could represent the most comprehensive information and summary about CRC metabolism to date. It certificates that metabolomics had great potential on both discovering clinical biomarkers and elucidating previously unknown mechanisms of CRC pathogenesis.

| S-EPMC5471069 | biostudies-literature

Potential role of microRNA-126 in the diagnosis of cancers: A systematic review and meta-analysis.

Project description:BackgroundCancer has become a major public concern all over the world and early diagnosis of cancer is of great benefit for treatment and prognosis. Several studies have investigated the association between abnormal circulating microRNA-126 (miR-126) expression and the risk of various cancers, but the results are inconsistent. Therefore, this meta-analysis was carried out to assess the potential diagnostic value of miR-126 for cancer.MethodsRelevant studies were searched from PubMed, Embase, and Web of Science and we calculated the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operator characteristic curve (AUC) to assess the diagnostic value of miR-126 for cancer detection.ResultsA total of 745 cancer patients and 749 controls from 11 studies of 7 papers were included in this meta-analysis. The summary estimates revealed that the pooled sensitivity was 68% (95% confidence interval [CI]: 60-75%), the specificity was 76% (95% CI: 65-85%), the PLR was 2.87 (95% CI: 1.96-4.21), the NLR was 0.42 (95% CI: 0.35-0.52), the DOR was 7 (95% CI: 4-11), and the AUC was 0.77 (95%CI: 0.73-0.80). Moreover, the sample type, cancer type, sample size, and quality score might be sources of heterogeneity.ConclusionThis systematic review and meta-analysis suggests that miR-126 has great potential to be a noninvasive biomarker in the diagnosis of cancer. However, more well-designed studies with larger sample size on the diagnostic value of miR-126 for cancer are needed in the future.

| S-EPMC5008569 | biostudies-literature

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