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Prognostic Value of MicroRNAs in Stage II Colorectal Cancer Patients: A Systematic Review and Meta-Analysis

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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.

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Acknowledgements

Our cancer research team would like to acknowledge the meta-analysis concepts and applications workshop manual by Michael Borenstein for detailed instructions and guidelines on reporting meta-analysis evaluation, subgroup analysis and publication bias detection (www.meta-analysis-workshops.com).

Author information

RJ and SS conceived this study and provided supervision and mentorship. SS led the development of the study and design, wrote the first draft of the article, and coordinated and integrated comments from co-authors. RJ, CK, MRM, AG, SB and SK revised and edited the final drafts and gave input to the final draft of the protocol. All the authors read, refined and approved the final version of the manuscript.

Correspondence to Rama Jayaraj.

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Conflict of interest

All authors (RJ, SS, CK, MRM, AG, SB and SK) have declared that there is no conflict of interest.

Funding

This research received no specific grant from any funding agency in public, commercial or not-for-profit sectors.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Fig 9 Legend: The black diamond represents the estimate of survival of miR215 expression in stage II colorectal cancer patients. The red line with the red square indicates the effect size of age of the selected study cohorts with a 95% confidence interval which cross the Black line are favours to death and Survival respectively. Fig 10 Legend: The black diamond represents the estimate of survival of miR143-5p expression in stage II colorectal cancer patients. The red line with the red square indicates the effect size of age of the selected study cohorts with a 95% confidence interval which cross the Black line are favours to death and Survival respectively. Fig 11 Legend: The black diamond represents the estimate of survival of miR106a expression in stage II colorectal cancer patients. The red line with the red square indicates the effect size of age of the selected study cohorts with a 95% confidence interval which cross the Black line are favours to death and Survival respectively. Fig 12 Legend: The black diamond represents the estimate of survival of miR415 expression in stage II colorectal cancer patients. The red line with the red square indicates the effect size of age of the selected study cohorts with a 95% confidence interval which cross the Black line are favours to death and Survival respectively (PDF 353 kb)

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Sabarimurugan, S., Madhav, M.R., Kumarasamy, C. et al. Prognostic Value of MicroRNAs in Stage II Colorectal Cancer Patients: A Systematic Review and Meta-Analysis. Mol Diagn Ther 24, 15–30 (2020). https://doi.org/10.1007/s40291-019-00440-y

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