scholarly journals A pair-wise meta-analysis highlights circular RNAs as potential biomarkers for colorectal cancer

2019 ◽  
Author(s):  
Chen Li ◽  
Xinli He ◽  
Lele Zhang ◽  
Lanying Li ◽  
Wenzhao Zhao

Abstract Background: Circular RNAs (circRNAs) have emerged as a special subset of endogenous RNAs that are implicated in tumorigenesis and cancer progression. Herein we aim to carry out a meta-analysis to evaluate the clinicopathologic, diagnostic and prognostic significance of circRNA expression in colorectal cancer (CRC). Methods: A systematic search of online databases was performed for original articles published in English, which investigated the diagnostic accuracy, prognostic utility, and clinicopathologic association of circRNA(s) in CRC. Data were strictly extracted and study bias was judged using the Quality Assessment for Studies of Diagnostic Accuracy II (QUADAS II) and Newcastle-Ottawa Scale (NOS) checklists. Results: A total of 13 studies, involving 1430 patients with CRC, were included in the meta-analysis. The clinicopathologic study showed that abnormally expressed circRNAs were correlated with tumor diameter (P = 0.0350), differentiation (P = 0.0038), lymphatic metastasis (P = 0.0119), distant metastasis (P < 0.0001), TNM stage (P = 0.0002), and depth of invasion (P=0.001) in patients with CRC. The summary area under the curve (AUC) of circRNA for the discriminative efficacy between patients with and without CRC was estimated to be 0.79, corresponding to a weighted sensitivity of 0.77 [95% confidence interval (CI): 0.74-0.79], specificity of 0.67 (95%CI: 0.64-0.70), and diagnostic odds ratio (DOR) of 7.52 (95%CI: 4.66-12.12). Survival analysis showed that highly expressed circRNAs were correlated with significantly worse overall survival (OS) [hazard ratio (HR) = 2.66, 95%CI: 2.03-3.50, P = 0.000; X2 = 4.34, P = 0.740, I2 = 0.0%], whereas lower expression of circRNAs was associated with prolonged OS (weighted HR=0.30, 95%CI: 0.17-0.53, P = 0.000; X2 = 1.34, P = 0.909, I2 = 0.0%). Stratified analysis in circRNA expression status, and test matrix also showed robust results. Conclusion: Abnormally expressed circRNAs may be auxiliary biomarkers facilitating CRC diagnosis, and promising prognostic biomarkers in predicting the survival of CRC patients.

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chen Li ◽  
Xinli He ◽  
Lele Zhang ◽  
Lanying Li ◽  
Wenzhao Zhao

Abstract Background Circular RNAs (circRNAs) have emerged as a special subset of endogenous RNAs that are implicated in tumorigenesis and cancer progression. Herein we aim to carry out a meta-analysis to evaluate the clinicopathologic, diagnostic and prognostic significance of circRNA expression in colorectal cancer (CRC). Methods A systematic search of online databases was performed for original articles published in English, which investigated the diagnostic accuracy, prognostic utility, and clinicopathologic association of circRNA(s) in CRC. Data were strictly extracted and study bias was judged using the Quality Assessment for Studies of Diagnostic Accuracy II (QUADAS II) and Newcastle-Ottawa Scale (NOS) checklists. Results A total of 13 studies, involving 1430 patients with CRC, were included in the meta-analysis. The clinicopathologic study showed that abnormally expressed circRNAs were correlated with tumor diameter (P = 0.0350), differentiation (P = 0.0038), lymphatic metastasis (P = 0.0119), distant metastasis (P < 0.0001), TNM stage (P = 0.0002), and depth of invasion (P = 0.001) in patients with CRC. The summary area under the curve (AUC) of circRNA for the discriminative efficacy between patients with and without CRC was estimated to be 0.79, corresponding to a weighted sensitivity of 0.77 [95% confidence interval (CI): 0.74–0.79], specificity of 0.67 (95%CI: 0.64–0.70), and diagnostic odds ratio (DOR) of 7.52 (95%CI: 4.66–12.12). Survival analysis showed that highly expressed circRNAs were correlated with significantly worse overall survival (OS) [hazard ratio (HR) = 2.66, 95%CI: 2.03–3.50, P = 0.000; X2 = 4.34, P = 0.740, I2 = 0.0%], whereas lower expression of circRNAs was associated with prolonged OS (weighted HR = 0.30, 95%CI: 0.17–0.53, P = 0.000; X2 = 1.34, P = 0.909, I2 = 0.0%). Stratified analysis in circRNA expression status, and test matrix also showed robust results. Conclusion Abnormally expressed circRNAs may be auxiliary biomarkers facilitating CRC diagnosis, and promising prognostic biomarkers in predicting the survival of CRC patients.


2019 ◽  
Author(s):  
Chen Li ◽  
Xinli He ◽  
Lele Zhang ◽  
Lanying Li ◽  
Wenzhao Zhao

Abstract Background: Circular RNAs (circRNAs) have emerged as a special subset of endogenous RNAs that are implicated in tumorigenesis and cancer progression. Herein we aim to carry out a meta-analysis to evaluate the clinicopathologic, diagnostic and prognostic significance of circRNA expression in colorectal cancer (CRC). Methods: A systematic search of online databases was performed for original articles published in English, which investigated the diagnostic accuracy, prognostic utility, and clinicopathologic association of circRNA(s) in CRC. Data were strictly extracted and study bias was judged using the Quality Assessment for Studies of Diagnostic Accuracy II (QUADAS II) and Newcastle-Ottawa Scale (NOS) checklists. Results: A total of 13 studies, involving 1430 patients with CRC, were included in the meta-analysis. The clinicopathologic study showed that abnormally expressed circRNAs were correlated with tumor diameter ( P = 0.0350), differentiation ( P = 0.0038), lymphatic metastasis ( P = 0.0119), distant metastasis ( P < 0.0001), TNM stage ( P = 0.0002), and depth of invasion ( P =0.001) in patients with CRC. The summary area under the curve (AUC) of circRNA for the discriminative efficacy between patients with and without CRC was estimated to be 0.79, corresponding to a weighted sensitivity of 0.77 [95% confidence interval (CI): 0.74-0.79], specificity of 0.67 (95%CI: 0.64-0.70), and diagnostic odds ratio (DOR) of 7.52 (95%CI: 4.66-12.12). Survival analysis showed that highly expressed circRNAs were correlated with significantly worse overall survival (OS) [hazard ratio (HR) = 2.66, 95%CI: 2.03-3.50, P = 0.000; X 2 = 4.34, P = 0.740, I 2 = 0.0%], whereas lower expression of circRNAs was associated with prolonged OS (weighted HR=0.30, 95%CI: 0.17-0.53, P = 0.000; X 2 = 1.34, P = 0.909, I 2 = 0.0%). Stratified analysis in circRNA expression status, and test matrix also showed robust results. Conclusion: Abnormally expressed circRNAs may be auxiliary biomarkers facilitating CRC diagnosis, and promising prognostic biomarkers in predicting the survival of CRC patients.


2020 ◽  
Author(s):  
Chenghao Zhang ◽  
Jieyu He ◽  
Lin Qi ◽  
Zhixi Duan ◽  
Lu Wan ◽  
...  

Abstract Background Circular RNAs (circRNAs) have emerged as pivotal regulators in osteosarcoma tumorigenesis and progression, but their prognostic and diagnostic significance remain unclear. Herein, we aimed to perform an updated meta-analysis to explore the clinical, diagnostic and prognostic values of circRNAs in osteosarcoma. Methods Several databases, including PubMed, Web of Science, EMBASE, Scopus and Cochrane Library, were systematically searched up to Mar 10, 2020. Eligible studies regarding the relationship between circRNAs levels and clinicopathological, diagnostic and prognostic values in osteosarcoma patients were included in this study. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to measure clinical characteristics, while hazard ratios (HRs) with 95% CIs were adopted to assess overall survival (OS) and disease-free survival (DFS). Results Overall, 26 relevant studies involving 1,652 patients with osteosarcoma were enrolled, with eighteen studies on clinicopathological parameters, ten on diagnosis and eighteen on prognosis. For clinical parameters, overexpression of oncogenic circRNAs was intimately correlated with larger tumor size (P <0.00001), advanced Enneking stage (P <0.00001), poor differentiation (P =0.0001), and distant metastasis (DM) (P <0.00001). In contrast, the downregulated circRNAs showed negative correlation with Enneking stage (P=0.002) and DM (P<0.0001). For the diagnostic values, the summary area under the curve (AUC) of circRNA for the discriminative efficacy between osteosarcoma patients and non-cancer counterparts was estimated to be 0.86 (95% CI: 0.83-0.89), with a weighted sensitivity of 0.80 (95% CI: 0.74-0.84), specificity of 0.80 (95%: 0.75-0.84), and diagnostic odds ratio (DOR) of 15.48 (10.85-22.10), respectively. For the prognostic significance, oncogenic circRNAs had poor OS (HR=1.92, 95% CI: 1.68-2.19) and DFS (HR=2.65, 95% CI: 2.02-3.49), while elevated expression of tumor-suppressor circRNAs were closely related to longer OS (HR=0.44, 95% CI: 0.28-0.69). Conclusions Taken together, our study showed that aberrantly expressed circRNA signatures could serve as potential predictive indicators in diagnosis and prognosis in patients with osteosarcoma.


2020 ◽  
Author(s):  
Chenghao Zhang ◽  
Jieyu He ◽  
Lin Qi ◽  
Zhixi Duan ◽  
Lu Wan ◽  
...  

Abstract Background CircRNAs have emerged as pivotal regulators in osteosarcoma tumorigenesis and progression, but their prognostic and diagnostic significance remain unclear. Herein, we aimed to perform an updated meta-analysis to explore the clinical, diagnostic and prognostic values of circRNAs in osteosarcoma. Methods Several databases, including PubMed, Web of Science, EMBASE, Scopus and Cochrane Library, were systematically searched up to April 10, 2020. Eligible studies regarding the relationship between circRNAs levels and clinicopathological, diagnostic and prognostic values in osteosarcoma patients were included in this study. Pooled odds ratios with corresponding 95% confidence intervals were used to measure clinical characteristics, while hazard ratios with 95% CIs were adopted to assess overall survival (OS) and disease-free survival (DFS). Results Overall, 26 relevant studies involving 1,652 patients with osteosarcoma were enrolled, with eighteen studies on clinicopathological parameters, ten on diagnosis and eighteen on prognosis. For clinical parameters, overexpression of oncogenic circRNAs was intimately correlated with larger tumor size (P < 0.00001), advanced Enneking stage (P < 0.00001), poor differentiation (P = 0.0001), and distant metastasis (DM) (P < 0.00001). In contrast, the downregulated circRNAs showed negative correlation with Enneking stage (P = 0.002) and DM (P < 0.0001). For the diagnostic values, the summary area under the curve of circRNA for the discriminative efficacy between osteosarcoma patients and non-cancer counterparts was estimated to be 0.86 (95% CI: 0.83–0.89), with a weighted sensitivity of 0.80 (95% CI: 0.74–0.84), specificity of 0.80 (95%: 0.75–0.84), and diagnostic odds ratio of 15.48 (10.85–22.10), respectively. For the prognostic significance, oncogenic circRNAs had poor OS (HR = 1.92, 95% CI: 1.68–2.19) and DFS (HR = 2.65, 95% CI: 2.02–3.49), while elevated expression of tumor-suppressor circRNAs were closely related to longer OS (HR = 0.44, 95% CI: 0.28–0.69). Conclusions Taken together, our study showed that aberrantly expressed circRNA signatures could serve as potential biomarkers in diagnosis and prognosis in patients with osteosarcoma.


2021 ◽  
Vol 20 ◽  
pp. 153303382110119
Author(s):  
Wen-Ting Zhang ◽  
Guo-Xun Zhang ◽  
Shuai-Shuai Gao

Background: Leukemia is a common malignant disease in the human blood system. Many researchers have proposed circulating microRNAs as biomarkers for the diagnosis of leukemia. We conducted a meta-analysis to evaluate the diagnostic accuracy of circulating miRNAs in the diagnosis of leukemia. Methods: A comprehensive literature search (updated to October 13, 2020) in PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang database and China National Knowledge Infrastructure (CNKI) was performed to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for diagnosing leukemia were pooled for both overall and subgroup analysis. The meta-regression and subgroup analysis were performed to explore heterogeneity and Deeks’ funnel plot was used to assess publication bias. Results: 49 studies from 22 publications with a total of 3,489 leukemia patients and 2,756 healthy controls were included in this meta-analysis. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the curve were 0.83, 0.92, 10.8, 0.18, 59 and 0.94, respectively. Subgroup analysis shows that the microRNA clusters of plasma type could carry out a better diagnostic accuracy of leukemia patients. In addition, publication bias was not found. Conclusions: Circulating microRNAs can be used as a promising noninvasive biomarker in the early diagnosis of leukemia.


2019 ◽  
Vol 14 (5) ◽  
Author(s):  
Sandra Viviana Muñoz Rodríguez ◽  
Herney Andrés García-Perdomo

Introduction: We aimed to determine the diagnostic accuracy of the prostate cancer antigen 3 (PCA3) test before performing the first biopsy compared with prostate biopsy for the diagnosis of prostate cancer. Methods: A systematic search was performed in MEDLINE, EMBASE, CENTRAL, LILACS, reference lists, specialized journals in urology and cancer, and unpublished literature. The population was adults with suspected prostate cancer, and the intervention was the measurement of PCA3 in urine samples for the diagnosis of prostate cancer. The quality of studies was evaluated with the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. The operative characteristics were determined, and a meta-analysis was performed. Results: Nine studies of diagnostic tests were included based on a cutoff value of 35. The following overall values were obtained: the sensitivity was 0.69 (95% confidence interval [CI] 0.61–0.75); specificity was 0.65 (95% CI 0.553–0.733); the diagnostic odds ratio (DOR) was 4.244 (95% CI 3.487–5.166); and the area under the curve was 0.734 (95% CI 0.674–0.805) with a heterogeneity of 0%. Conclusions: Urinary PCA3 has an acceptable diagnostic accuracy, aids in the study of patients with suspected prostate cancer, and can be used as a guide for directing the performance of the first prostate biopsy and decreasing unnecessary biopsies.


2020 ◽  
Author(s):  
Jinpeng Yuan ◽  
Dongming Guo ◽  
Xinxin Li ◽  
Juntian Chen

Abstract Background: Circular RNAs (circRNAs) are new stars in the network of noncoding RNAs and are regarded as key control factors in numerous tumours. The purpose of our study was to evaluate the clinical, prognostic and diagnostic role of circRNAs in colorectal cancer. The quality of all the articles were assessed by the Newcastle‐Ottawa Scale. Methods: An online search in electronic databases, including the PubMed, Cochrane Library and Web of Science online databases, was conducted to identify as many relevant papers as possible. Nineteen relevant studies were enrolled in this meta-analysis, with seven on diagnosis, eight on prognosis and 11 on clinicopathological features. Results: For the diagnostic value of circRNAs, the pooled results showed that the area under the curve (AUC) was 0.82 for identifying patients with colorectal cancer, with a sensitivity of 83% and a specificity of 72%. In terms of prognosis, carcinogenic circRNAs have a negative effect on overall survival (OS: HR = 2.29, 95% CI: 1.50-3.52), and increases in tumour suppressor circRNA expression are associated with longer survival (OS: HR = 0.37, 95% CI: 0.22-0.64). And the elevated expression of oncogenic circRNAs is associated with poor clinical features while tumor suppressor circRNAs are the complete opposite. Conclusions: These results suggest that circRNAs may be a potential biomarker for the diagnosis and prognosis of colorectal cancer.


2020 ◽  
Vol 93 (1109) ◽  
pp. 20190847 ◽  
Author(s):  
Pankaj Gupta ◽  
Varun Bansal ◽  
Praveen Kumar-M ◽  
Saroj K Sinha ◽  
Jayanta Samanta ◽  
...  

Objective: To evaluate the sensitivity, specificity, and diagnostic odds ratio (DOR) of Doppler ultrasound, CT, and MRI in the diagnosis of Budd Chiari syndrome (BCS). Methods: We performed a literature search in PubMed, Embase, and Scopus to identify articles reporting the diagnostic accuracy of Doppler ultrasound, CT, and MRI (either alone or in combination) for BCS using catheter venography or surgery as the reference standard. The quality of the included articles was assessed by using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results: 11 studies were found eligible for inclusion. Pooled sensitivities and specificities of Doppler ultrasound were 89% [95% confidence interval (CI), 81–94%, I2 = 24.7%] and 68% (95% CI, 3–99%, I2 = 95.2%), respectively. Regarding CT, the pooled sensitivities and specificities were 89% (95% CI, 77–95%, I2 = 78.6%) and 72% (95% CI, 21–96%, I2 = 91.4%), respectively. The pooled sensitivities and specificities of MRI were 93% (95% CI, 89–96%, I2 = 10.6%) and 55% (95% CI, 5–96%, I2 = 87.6%), respectively. The pooled DOR for Doppler ultrasound, CT, and MRI were 10.19 (95% CI: 1.5, 69.2), 14.57 (95% CI: 1.13, 187.37), and 20.42 (95% CI: 1.78, 234.65), respectively. The higher DOR of MRI than that of Doppler ultrasound and CT shows the better discriminatory power. The area under the curve for MRI was 90.8% compared with 88.4% for CT and 86.6% for Doppler ultrasound. Conclusion: Doppler ultrasound, CT and MRI had high overall diagnostic accuracy for diagnosis of BCS, but substantial heterogeneity was found. Prospective studies are needed to investigate diagnostic performance of these imaging modalities. Advances in knowledge: MRI and CT have the highest meta-analytic sensitivity and specificity, respectively for the diagnosis of BCS. Also, MRI has the highest area under curve for the diagnosis of BCS.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jiangbi Li ◽  
Xiaoping Xie ◽  
Weibing Liu ◽  
Feng Gu ◽  
Ke Zhang ◽  
...  

Background: Abnormal expression levels of microRNAs (miRNAs) were observed in ankylosing spondylitis (AS) in recent articles, suggesting that miRNAs may be used as biomarkers for AS diagnoses. In this paper, we conducted a meta-analysis to identify the overall diagnostic accuracy of miRNA biomarkers in AS patients.Methods: An extensive search was undertaken in PubMed, Embase, Cochrane databases, and Wan Fang database up to 30 December 2020 using the following key words: (“microRNAs” or “microRNA” or “miRNA” or “miR” or “RNA, Micro” or “Primary MicroRNA”) and (“Spondylitis Ankylosing” or “Spondyloarthritis Ankylopoietica” or “Ankylosing Spondylarthritis” or “Ankylosing Spondylarthritides” or “Spondylarthritides Ankylosing” or “Ankylosing Spondylitis”) and (“blood” or “serum” or “plasma”). Statistical evaluation of dysregulated miRNAs using the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC).Results: Twenty-nine articles reporting on the miRNAs of AS were included. A total of 42 miRNAs were observed to be up-regulated and 45 miRNAs were down-regulated in the AS cases compared with the controls. Besides, 29 studies from nine articles were included in our meta-analysis. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0. 76 (95% CI, 0.70–0.81), 0.80 (95% CI, 0.74–0.85), 3.75 (95% CI, 2.82–5.01), 0.30 (95% CI, 0.24–0.39), 12.32 (95% CI, 7.65–19.83), 0.85 (95% CI, 0.81–0.88), respectively, suggesting a good diagnostic accuracy of miRNAs for AS.Conclusions: Circulating miRNAs are deregulated in AS patients. miRNAs may be used as a relatively non-invasive biomarkers for the detection of AS.


2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Changhua Zhuo ◽  
Xianyi Wu ◽  
Jing Li ◽  
Dan Hu ◽  
Jinliang Jian ◽  
...  

Chemokine (C-X-C motif) ligand 1 (CXCL1) is a chemotactic cytokine known to regulate cancer progression and invasion. However, the prognostic significance of CXCL1 expression in colorectal cancer (CRC) has not been fully characterized. The present study explored the clinicopathological significance and potential role of CXCL1 in the carcinogenesis and progression of CRC. The protein expression of CXCL1 was measured immunohistochemically in tissue microarrays constructed from 276 CRC patients. CXCL1 expression levels and their associations with clinicopathological characteristics and patient survival were evaluated. The effect of CXCL1 on glycolysis was also examined. High CXCL1 expression was detected in 165 (59.8%) cases. CXCL1 expression was correlated with tumor diameter (P=0.002), T stage (P=0.044), N stage (P=0.005), M stage (P=0.001), lymphovascular invasion (P=0.010), and carcinoembryonic antigen status (P=0.019). High CXCL1 expression was validated as an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) by both univariate and multivariate Cox regression analyses (both P<0.05). Experimentally, expression of CXCL1 was knocked down by stable transfected short hairpin RNA, resulting in a significantly decreased rate of glycolysis both in in vitro assays and in patients’ samples (P<0.05). Silencing the expression of CXCL1 decreased the levels of the glycolytic enzymes GLUT1, HK2, and LDHA. In conclusion, by inducing glycolysis, CXCL1 plays a crucial role in both cancer progression and metastasis in CRC patients. The CXCL1 expression level is an independent prognostic factor for both OS and DFS. Moreover, CXCL1 may serve as a new biomarker and potential therapeutic target for CRC treatment.


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