Background: The neutrophil-lymphocyte-ratio, platelet-lymphocyte-ratio, and monocyte-lymphocyte-ratio have been explored as a simple, inexpensive, and effective method for cancer prognosis. However, there are no studies that have investigated the comparative utility of these markers, in multiple cancers. Methods: The preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) guidelines were used to design this meta-analysis protocol. The final study will also be conducted under the PRISMA guidelines for systematic reviews and meta-analyses. The core bibliographic database search will be carried out by 2 reviewers working individually, with each conducting an initial screening based on titles and abstracts. The shortlisted articles will be selected for review and quantitative analysis, based on predefined inclusion and exclusion criteria. Study characteristics, relevant clinicopathological characteristics, and statistical data required for meta-analysis (hazard ratios [HRs] and 95% confidence intervals [CIs]) will be extracted and compiled into a MS Excel datasheet. Meta-analysis will be performed, using a random-effects model, and the results (pooled HR and 95% CI) will be presented in the form of a forest plot. Publication bias will also be assessed by use of Egger bias indicator test and funnel plot symmetry. If statistical data from included studies is insufficient, a qualitative literature review will be pursued. PROSPERO registration: PROSPERO CRD42019121008.

Head and Neck Cancer (HNC) is the sixth most common type of cancer across the globe, with more than 300,000 deaths each year, globally. However, there are currently no standardised molecular markers that assist in determining HNC prognosis. The literature for this systematic review and meta-analysis were sourced from multiple bibliographic databases. This review followed PRISMA guidelines. The Hazard Ratio (HR) was selected as the effect size metric to independently assess overall survival (OS), disease-free survival (DFS), and prognosis. Subgroup analysis was performed for individual highly represented miRNA. A total of 6843 patients across 50 studies were included in the systematic review and 34 studies were included in the meta-analysis. Studies across 12 countries were assessed, with China representing 36.7% of all included studies. The analysis of the survival endpoints of OS and DFS were conducted separately, with the overall pooled effect size (HR) for each being 1.825 (95% CI 1.527–2.181; p < 0.05) and 2.596 (95% CI 1.917–3.515; p < 0.05), respectively. Subgroup analysis was conducted for impact of miR-21, 200b, 155, 18a, 34c-5p, 125b, 20a and 375 on OS, and miR-21 and 34a on DFS. The pooled results were found to be statistically significant for both OS and DFS. The meta-analysis indicated that miRNA alterations can account for an 82.5% decrease in OS probability and a 159.6% decrease in DFS probability. These results indicate that miRNAs have potential clinical value as prognostic biomarkers in HNC, with miR-21, 125b, 34c-5p and 18a, in particular, showing great potential as prognostic molecular markers. Further large scale cohort studies focusing on these miRNAs are recommended to verify the clinical utility of these markers individually and/or in combination.

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Awareness of breast cancer has been increasing due to early detection, but the advanced disease has limited treatment options. There has been growing evidence on the role of miRNAs involved in regulating the resistance in several cancers. We performed a comprehensive systematic review and meta-analysis on the role of miRNAs in influencing the chemoresistance and sensitivity of breast cancer. A bibliographic search was performed in PubMed and Science Direct based on the search strategy, and studies published until December 2018 were retrieved. The eligible studies were included based on the selection criteria, and a detailed systematic review and meta-analysis were performed based on PRISMA guidelines. A random-effects model was utilised to evaluate the combined effect size of the obtained hazard ratio and 95% confidence intervals from the eligible studies. Publication bias was assessed with Cochran’s Q test, I2 statistic, Orwin and Classic fail-safe N test, Begg and Mazumdar rank correlation test, Duval and Tweedie trim and fill calculation and the Egger’s bias indicator. A total of 4584 potential studies were screened. Of these, 85 articles were eligible for our systematic review and meta-analysis. In the 85 studies, 188 different miRNAs were studied, of which 96 were upregulated, 87 were downregulated and 5 were not involved in regulation. Overall, 24 drugs were used for treatment, with doxorubicin being prominently reported in 15 studies followed by Paclitaxel in 11 studies, and 5 drugs were used in combinations. We found only two significant HR values from the studies (miR-125b and miR-4443) and our meta-analysis results yielded a combined HR value of 0.748 with a 95% confidence interval of 0.508–1.100; p-value of 0.140. In conclusion, our results suggest there are different miRNAs involved in the regulation of chemoresistance through diverse drug genetic targets. These biomarkers play a crucial role in guiding the effective diagnostic and prognostic efficiency of breast cancer. The screening of miRNAs as a theragnostic biomarker must be brought into regular practice for all diseases. We anticipate that our study serves as a reference in framing future studies and clinical trials for utilising miRNAs and their respective drug targets.

BackgroundNasopharyngeal cancer (NPC), despite being one of the most malignant head and neck carcinomas (HNC), lacks comprehensive prognostic biomarkers that predict patient survival. Therefore, this systematic review and meta-analysis is aimed to evaluate the potential prognostic value of miRNAs as prognostic biomarkers in NPC.MethodsPRISMA guidelines were used to conduct this systematic review and meta-analysis study. Permutations of multiple “search key-words” were used for the search strategy, which was limited to articles published between January 2012 and March 2018. The retrieved articles were meticulously searched with multi-level screening by two reviewers and confirmed by other reviewers. Meta-analysis was performed using Hazard Ratios (HR) and associated 95% Confidence Interval (CI) of survival obtained from previously published studies. Publication bias was assessed by Egger’s bias indicator test and funnel plot symmetry.ResultsA total of 5069 patients across 21 studies were considered eligible for inclusion in the systematic review, with 65 miRNAs being evaluated in the subsequent meta-analysis. Most articles included in this study originated from China and one study from North Africa. The forest plot was generated using cumulated survival data, resulting in a pooled HR value of 1.196 (95% CI: 0.893–1.601) indicating that the upregulated miRNAs increased the likelihood of death of NPC patients by 19%.ConclusionTo our knowledge, this is the first meta-analysis that examines the prognostic effectiveness of miRNAs as biomarkers in NPC patients. We noted that the combined effect estimate of HR across multiple studies indicated that increased miRNA expression in NPC potentially leads to poor overall survival. However, further large-scale prospective studies on the clinical significance of the miRNAs, with sizable cohorts are necessary in order to obtain conclusive results.