Advancing gastrointestinal cancer diagnostics: a systematic review and meta-analysis of circulating microRNA-1246 as a non-invasive biomarker.

BACKGROUND: Despite numerous reports on the alterations of microRNA-1246 (miR-1246) expression level in digestive system cancers, its role in gastrointestinal cancers (GICs) remains unclear. This meta-analysis aimed to assess the diagnostic potential of circulating miR-1246 in GICs. METHODS: Meta-disc version 1.4 and Comprehensive Meta-Analysis (CMA) version 3.7 software were used to calculate pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), area under the curve (AUC), Q*index and summary receiver-operating characteristic (SROC). Subgroup analyses were conducted for cancer type, sample type and geographical region. Publication bias was assessed using Begg's and Egger's tests. RESULTS: A total of 14 articles involving 18 studies and 1526 participants (972 cases and 554 controls) were included. The diagnostic accuracy of miRNA-1246 in GICs was as follows: pooled sensitivity: 0.81 (95% CI: 0.79 - 0.83), specificity: 0.74 (95% CI: 0.71 - 0.77), PLR: 3.315 (95% CI: 2.33 - 4.72), NLR: 0.221 (95% CI: 0.153 - 0.319), DOR: 16.87 (95% CI: 9.45 - 30.09), AUC: 0.891, and Q*-index: 0.807. No publication bias was found based on Begg's (p = 0.172) and Egger's (p = 0.113) tests. CONCLUSION: Circulating miR-1246 shows promise as a non-invasive biomarker for early detection of GICs.

Diagnostic performance of fluorescence in situ hybridization (FISH) in upper tract urothelial carcinoma (UTUC): a systematic review and meta-analysis.

BACKGROUND: Fluorescence in situ hybridization (FISH) is a technique that uses fluorescently labeled DNA probes. Many studies have evaluated the ROC curve (sensitivity and specificity) with the FISH method to diagnose upper tract urothelial carcinoma (UTUC). The current meta-analysis was performed to examine the diagnostic power of the FISH method in UTUC. METHODS: We reviewed databases and methodically obtained papers for analysis until April 25th, 2022. The Meta-disc V.1.4 and Comprehensive Meta-Analysis V.3.3 software calculated the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, area under the curve (AUC), and summary receiver-operating characteristic (SROC). The I2 and Chi-square tests were used to examine the heterogeneity. Finally, the publication bias was estimated using Begg's and Egger's tests. RESULTS: A total of 13 articles included 1,067 participants (439 cases and 628 controls). The overall pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.72 (95% CI 0.67-0.76), 0.95 (95% CI 0.93-0.97), 10.42 (95% CI 5.84-18.60), 0.29 (95% CI 0.21-0.40), 38.55 (95% CI 18.58-79.96), and 0.91, respectively. No publication bias was reported based on Begg's and Egger's tests (Begg's p = 0.200; Egger's p = 0.151). CONCLUSION: This paper clearly shows that the high specificity and acceptable sensitivity of the FISH method make it a promising diagnostic method for UTUC in urine samples. However, further research with higher statistical numbers is needed to strengthen the correlation and be used for diagnostic applications.

Investigating angiogenin/ribonuclease 5 as a diagnostic biomarker for bladder cancer: In-depth analysis from a systematic review and meta-analysis.

Bladder cancer (BC) represents a prevalent malignancy in North America and Europe, posing significant health burdens. The identification of a reliable biomarker for early BC detection is imperative to enhance prognostic outcomes. Our aim for this study is to determine the diagnostic accuracy and potential clinical utility of Angiogenin/Ribonuclease 5 (ANG/RNase 5) as a biomarker for detection of BC. A systematic literature search across multiple databases up to March 20, 2024, was conducted. CMA 3.7 and Meta-disk 1.4 were used to analyze specificity, sensitivity, AUC, DOR, LR+, LR-, Q*index, and SROC for ANG as a urinary biomarker in BC patients. Publication bias was assessed using Egger's regression asymmetry and Begg's rank correlation tests. Additional diagnosing analyses were performed using Python programming language version 3.12.1. In this meta-analysis of seven case-control studies comprising 1,051 participants (576 cases and 481 controls), pooled sensitivity was 0.701 (95 % CI: 0.662-0.738), specificity was 0.787 (95 % CI: 0.752-0.819), LR + was 3.582 (95 % CI: 2.260-5.676), LR- was 0.398 (95 % CI: 0.327-0.485), and DOR was 10.637 (95 % CI: 6.106-18.529). The AUC and Q* index values were 0.823 and 0.756, respectively. Both Begg and Mazumdar Rank Correlation Test (p = 0.229) and Egger's Test of the Intercept (p = 0.135) revealed no significant evidence of publication bias. Our meta-analysis confirms ANG/RNase 5 as a reliable biomarker for early bladder cancer detection, showing strong diagnostic accuracy and no publication bias.

Gastric Cancer and Circulating microRNAs: An Updated Systematic Review and Diagnostic Meta-Analysis.

BACKGROUND: Circulating microRNAs (miRNAs, miRs) are now used as noninvasive diagnostic indicators in various malignancies. OBJECTIVE: Our objective is to use a meta-analysis to assess the diagnostic performance of circulating miRNAs in gastric cancer. METHODS: We reviewed databases and methodically obtained papers for analysis until October 15th, 2021. The random-effect meta-analysis was performed to construct pooled diagnostic parameters. To detect the causes of heterogeneity, spearman threshold effect analysis and subgroup analysis were performed. The I2 and Chi-square tests were also used to examine the heterogeneity. The subgroup analyses were conducted based on sample types (serum/plasma/blood), normalized genes (U6, miR-16, and miR-39), qPCR mastermix (SYBR and Taqman), and country. Finally, the publication bias was estimated using Egger's funnel plot asymmetry test. RESULTS: A total of 40 articles covering 73 studies (59 microRNAs) were included, containing 11,022 participants (6,324 cases and 4,698 controls). The overall pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.75 (95% CI: 0.74-0.77), 0.79 (95% CI: 0.78-0.80), 4.081 (95% CI: 3.43-4.85), 0.28 (95% CI: 0.25-0.32), 16.08 (95% CI: 12.34-20.95), and 0.877 (CI: 0.84-0.90), respectively. We conducted a subgroup analysis of diagnostic values, which revealed that serum type, U6 reference gene, SYBR mastermix, and East Asian Countries (China and Japan) had better diagnostic value. CONCLUSION: Circulating miRs can serve as diagnostic biomarkers for gastric cancer. However, specific miRNAs still need to be discovered in diagnosing gastric cancer, especially early screening.

Can microRNAs be utilized as tumor markers for recurrence following nephrectomy in renal cell carcinoma patients? A meta-analysis provides the answer.

INTRODUCTION: Renal cell carcinoma (RCC) is an aggressive tumor. Many studies investigated microRNAs (miRs) as RCC prognostic biomarkers, often reporting inconsistent findings. We present a meta-analysis to identify if tissue-derived miRs can be used as a prognostic factor in patients after nephrectomy. METHODS: Data were obtained from PubMed, Embase, and Web of Science. The hazard ratio with 95% confidence intervals assessed the prognostic value of microRNAs. Outcomes of interest included the prognosis role of microRNAs in overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS) in nephrectomy patients. RESULTS: Nine retrospective studies that evaluated microRNAs in 1,541 nephrectomy patients were collected. There were heterogeneities across studies for microRNAs in the 15 studies examining OS, RFS, and CSS (I2 = 84.51%; P < 0.01); the random-effect model was calculated (HR = 1.371; (95% CI: 0.831-2.260); P = 0.216). CONCLUSION: Our study indicated that miRNAs cannot be used as a marker for recurrence in RCC patients after nephrectomy, and researchers shouldn't make the mistake that if miRs can be used as a biomarker in RCC, they cannot be used as a marker after nephrectomy in RCC. As all of these findings were from retrospective studies, further studies are needed to verify the role of microRNAs in clinical trials.

Apolipoprotein A-1 as a Potential Biomarker for Solid Tumors: A Systematic Review and Meta-Analysis.

BACKGROUND: The diagnostic value of apolipoprotein A-I (ApoA-I) as a marker of different malignancies has been reported in several investigations; however, the results have been contradictory. The current meta-analysis examined the association between ApoA-I levels and human malignancies. METHODS: We reviewed the databases and retrieved papers for analysis until November 1st, 2021. Random-effects meta-analysis was performed to construct the pooled diagnostic parameters. To find the causes of heterogeneity, we utilized Spearman threshold effect analysis and subgroup analysis. The I² and Chi-square tests were used to examine the heterogeneity. Moreover, subgroup analyses were performed based on sample type (serum/urine) and geographical region of study. Finally, publication bias was explored using Begg's and Egger's tests. RESULTS: A total of 11 articles involving 4,121 participants (2,430 cases and 1,691 controls) were included. The overall pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.764 (95% CI: 0.746 - 0.781), 0.795 (95% CI: 0.775 - 0.814), 5.105 (95% CI: 3.313 - 7.865), 0.251 (95% CI: 0.174 - 0.364), 24.61 (95% CI: 12.22 - 49.54), and 0.93, respectively. In subgroup analyses, better diagnostic values were found for urine samples and East Asian Countries (China, Korea, and Taiwan). CONCLUSION: Urinary ApoA-I levels may serve as a favorable diagnostic marker for cancer.

Detection of Circulating Cell-Free DNA to Diagnose Hepatocellular Carcinoma in Chinese Population: A Systematic Review and Meta-Analysis.

BACKGROUND: Cell-free circulating DNA has been known for many years, but this knowledge has not been beneficial for diagnosis. In this meta-analysis, we examine the diagnostic role of circulating cell-free DNA in HCC patients to find a reliable biomarker for the early detection of HCC. MATERIALS AND METHODS: We performed a systematic literature search using Science Direct, Web of Science, PubMed/Medline, Scopus, Google Scholar, and Embase, up to April 1st, 2022. Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.3.3 software calculated the pooled specificity, sensitivity, area under the curve (AUC), diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR) Q*index, and summary receiver-operating characteristic (SROC) for the role of cfDNA as a biomarker for HCC patients. Moreover, the subgroup analyses have been performed based on sample types (serum/plasma) and detection methods (MS-PCR/methylation). RESULTS: A total of 7 articles (9 studies) included 697 participants (485 cases and 212 controls). The overall pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.706 (95% CI: 0.671 - 0.739), 0.905 (95% CI: 0.865 - 0.937), 6.66 (95% CI: 4.36 - 10.18), 0.287 (95% CI: 0.185 - 0.445), 28.40 (95% CI: 13.01 - 62.0), and 0.93, respectively. We conducted a subgroup analysis of diagnostic value, which showed that the plasma sample had a better diagnostic value compared to the serum. CONCLUSION: This meta-analysis showed that cfDNA could be a fair biomarker for diagnosing HCC patients.

Diagnostic accuracy of tumor M2-pyruvate kinase (tM2-PK) as a non-invasive biomarker in colorectal cancer: A systematic review and meta-analysis.

INTRODUCTION: The tumor pyruvate kinase M2 isoform (tM2-PK) is a glycolytic enzyme isoform that is present on the surface of rapidly proliferating cancer cells. The objective of this investigation was to assess the efficacy of the tM2-PK measurement assay in detecting colorectal cancer (CRC) through the analysis of serum/plasma and stool samples obtained from patients. METHODS: The pooled diagnostic performance measures, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), the area under the curve (AUC), Q*index, and summary receiver-operating characteristic curve (SROC), were computed using the Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.3.3 software. The statistical methods of I2 and chi-square were employed to assess the presence of heterogeneity. The estimation of publication bias was conducted through the implementation of Begg's rank correlation and Egger's regression asymmetry tests. RESULTS: A total of 28 studies were found, involving 2900 participants (1560 cases and 1340 controls). The diagnostic accuracy of tM2-PK was calculated in CRC based on the pooled sensitivity of 83.70% (95% CI: 82.0% - 85.30%), specificity of 74.0% (95% CI: 72.0% - 76.0%), PLR of 4.432 (95% CI: 3.33 - 5.60), NLR of 0.187 (95% CI: 0.144 - 0.243), DOR of 30.182 (95% CI: 19.761 - 46.10) as well as AUC at 91.6%, and Q*-index at 85.0%. Publication bias was seen based on Begg's (p = 0.0006) and Egger's (p = 0.00015) tests. CONCLUSION: The results demonstrate that tM2-PK exhibits promise as a fair marker for CTRC, with the potential to serve as a non-invasive biomarker.

Blood-based microRNAs as Potential Diagnostic biomarkers for Melanoma: A Meta-analysis.

INTRODUCTION: Circulating microRNAs (miRNAs) serve as noninvasive diagnostic markers in many cancers. This meta-analysis aims to evaluate the diagnostic efficacy of circulating microRNAs for melanoma. MATERIAL AND METHODS: The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and ROC curve were evaluated using the Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.3.3 software packages. To investigate the heterogeneity, the I2 and Chi-square tests were used. The publishing bias was evaluated using Begg's rank correlation and Egger regression asymmetry tests. RESULTS: A total of 9 articles covering 13 studies (more than 50 miRs individually and in combination) were included, containing 1,355 participants (878 cases and 477 controls). The overall pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and AUC were 0.78 (95% CI: 0.76-0.81), 0.80 (95% CI: 0.77-0.83), 4.32 (95% CI: 3.21-5.82), 0.17 (95% CI: 0.09-0.32), 28.0 (95% CI: 15.34-51.09), and 0.91, respectively. According to Begg's and Egger's tests, there was no publication bias (Begg's p = 0.160 and Egger's p = 0.289). CONCLUSION: Circulating miRNAs can serve as fair and non-invasive diagnostic biomarkers for melanoma. Additionally, specific miRNAs still need to be discovered for diagnosing melanoma.

Previous pulmonary tuberculosis enhances the risk of lung cancer: systematic reviews and meta-analysis.

PURPOSE: The possible association between history of pulmonary tuberculosis (TB) and lung cancer (LC) has attracted researchers' attention for several decades. This systematic review and meta-analysis aim to assess the association between previous pulmonary TB infection and LC risk. METHODS: A Systematic and comprehensive search was performed in the following databases: PubMed, Embase, clinical key, Web of Science and Google Scholar, in articles and abstracts published from 1987 to 2021. Thirty-two articles (involving 50,290 cases and 846,666 controls) met the inconclusive criteria. The Comprehensive Meta-Analysis version 2.2 software was used for this meta-analysis. RESULTS: The result of this meta-analysis demonstrates that pre-existing active pulmonary TB increases the risk of LC (RR = 2.170, 95% confidence interval [CI] 1.833-2.569, p < .001, I2 = 91.234%). The results showed that the risk of the history of active pulmonary TB infection in adenocarcinoma was 2.605 (95% CI 1.706-3.979, p < .001, I2 = 55.583%), in small-cell carcinoma was 2.118 (95% CI 1.544-2.905, p < .001, I2 = 0.0%), in squamous-cell carcinoma, was 3.570 (95% CI 2.661 - 4.791, p < .001, I2 = 42.695%) and 2.746 (95% CI 2.300-3.279, p < .001, I2 = 41.686%) for other histological types of LCs. According to these results, a history of active pulmonary TB increases the risk of LC. CONCLUSIONS: This study emphasizes the importance of LC screening in pulmonary TB patients even after the infection is treated. With the increased chances of LC in a patient who had a history of active pulmonary TB, there could be a need for a further follow-up period after pulmonary TB recovery.