ABSTRACT
BACKGROUND: We performed a systematic review and meta-analysis to identify and underline multiple microRNAs (miRNAs) as biomarkers of disease prognosis in stage II colorectal cancer (CRC) patients. METHODS AND ANALYSIS: This systematic review and meta-analysis study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The required articles were collected from online bibliographic databases from January 2011 to November 2019 with multiple permutation keywords. Quantitative data synthesis was based on a meta-analysis with pooled data to observe and analyse the outcome measures and effect estimates by using the random effect model. The subgroup analysis was performed from demographic characteristics and the available data. RESULTS: Eighteen articles were included in this study, 16 of which were incorporated for meta-analysis to examine the stage II CRC prognosis with up- and downregulated miRNA expressions. The pooled hazard ratio (HR) for death in stage II CRC patients was 1.90 (95% confidence interval 1.63-2.211), with a significant p value. A subgroup analysis based on up- or downregulated miRNA expression individually and any deregulated miRNA was also associated with a worse prognosis. The subgroup analysis included parameters such as age, gender, stage II and III combined patients' survival and the repetitive miRNAs (miR21, miR215, miR143-5p, miR106a and miR145) individually. CONCLUSION: MicroRNAs play a significant role in determining prognosis in stage II CRC patients, with upregulation of miR21, miR215, miR143-5p and miR106a, in particular, portending a worse prognosis. These miRNAs could be considered for further evaluation as biomarkers of prognosis and to guide the decision to administer adjuvant chemotherapy.
Subject(s)
Biomarkers, Tumor , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , MicroRNAs/genetics , Colorectal Neoplasms/mortality , Colorectal Neoplasms/therapy , Computational Biology/methods , Gene Expression Regulation , Genetic Heterogeneity , Humans , Neoplasm Staging , Prognosis , Proportional Hazards Models , Publication Bias , Sex FactorsSubject(s)
Oropharyngeal Neoplasms , Papillomaviridae/genetics , Papillomavirus Infections , DNA , HumansABSTRACT
BACKGROUND: Human epididymis protein 4 (HE4) protein has garnered a great degree of interest as a complementary biomarker to carbohydrate antigen 125 (CA125), or even as an independent biomarker for monitoring, diagnosis, and prognostication of ovarian cancer. Its use is currently limited to ovarian cancer. Recent studies have suggested that it could also be used in other types of cancers. METHODS: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines was 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 statistical 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 interval [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 data are insufficient, a narrative line of review will be pursued. DISCUSSION: HE4 protein has been shown to have great potential for clinical use as a diagnostic and prognostic marker in epithelial ovarian cancer (EOC). However, HE4 is not only limited to expression in ovarian cancer, but is also overexpressed in lung and endometrial cancers. The effectiveness of HE4 as a biomarker in cancers (other than EOC) has not yet been studied in the form of a comprehensive systematic review and meta-analysis. The results of this study should allow for expanded use of HE4 as a multiutility biomarker in multiple cancer types, thereby, elevating HE4's value as a cancer biomarker. PROSPERO REGISTRATION: CRD42019120326.
Subject(s)
Carcinoma/diagnosis , Carcinoma/metabolism , Meta-Analysis as Topic , Proteins/metabolism , Systematic Reviews as Topic , Biomarkers, Tumor/metabolism , Humans , Prognosis , Research Design , WAP Four-Disulfide Core Domain Protein 2ABSTRACT
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.
Subject(s)
Biomarkers, Tumor , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/mortality , MicroRNAs/genetics , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/pathology , Humans , Prognosis , Publication Bias , RNA InterferenceSubject(s)
Papillomavirus Infections , Penile Neoplasms , Cyclin-Dependent Kinase Inhibitor p16 , DNA , Humans , Male , PrevalenceSubject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Humans , Lymph Node Excision , Lymph Node Ratio , Lymph Nodes , PrognosisABSTRACT
BACKGROUND: Breast Cancer (BC) is the leading cause of deaths in Indian women. Emerging reports reveal alarming evidence of increasing incidence and mortality of BC among young Indian women in addition to the late presentation and poor prognosis. Despite the significant incidence, there is a lack of reliable data resources and comprehensive epidemiologic studies relating to BC. The objective of this protocol is to conduct a full-scale systematic review and meta-analyses on the incidence, prevalence, and mortality of BC in 29 states and seven union territories of India. METHODS: Data sources used will be Cochrane Review, MEDLINE, PubMed, Scopus, Science Direct, Web of Science, and international and national cancer registries such as World Health Organization, International Agency for Research on Cancer (IARC), and National Centre for Disease Information and Research (NCDIR)-National Cancer Registry Program initiated by Indian Council of Medical Research. Relevant data will be extracted using a predefined data collection form. A defined search strategy will be implemented along with selection criteria to obtain full-text articles of relevant studies. This study protocol was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Protocols 2015 guidelines. Odds ratios (ORs) will be used to measure effect size. The random or fixed-effects meta-analyses model will be employed to aggregate the pooled estimates (ORs) with 95% confidence intervals (CIs) separately. A forest plot will be produced to assess ORs and 95% CIs. Publication bias will be assessed using funnel plot, and Egger regression will be applied to test the symmetry of the funnel plot. ETHICS AND DISSEMINATION: This proposed study will be based on published studies and the data from cancer registries. Therefore, human research ethics approval is not required. The results of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NO: CRD42018084003.
