Molecular Diagnosis & Therapy

, Volume 23, Issue 1, pp 65–82 | Cite as

Current Evidence on miRNAs as Potential Theranostic Markers for Detecting Chemoresistance in Colorectal Cancer: A Systematic Review and Meta-Analysis of Preclinical and Clinical Studies

  • Madhav Madurantakam Royam
  • Chellan Kumarasamy
  • Siddhartha Baxi
  • Ajay Gupta
  • Nachimuthu Ramesh
  • Gothandam Kodiveri Muthukaliannan
  • Rama JayarajEmail author
Systematic Review



Findings from observational clinical studies examining the relationship between biomarker expression and theranosis in colorectal cancer (CRC) have been conflicting.


We conducted this systematic review and meta-analysis to summarise the existing evidence to demonstrate the involvement of microRNAs (miRNAs) in chemoresistance and sensitivity in CRC through drug genetic pathways.


Using PRISMA guidelines, we systematically searched PubMed and Science Direct for relevant studies that took place between 2012 and 2017. A random-effects model of meta-analysis was applied to evaluate the pooled effect size of hazard ratios (HRs) across the included studies. Cochran’s Q test and the I2 statistic were used to detect heterogeneity. A funnel plot was used to assess potential publication bias.


Of the 4700 studies found, 39 studies comprising 2822 patients with CRC met the inclusion criteria. The included studies used one or a combination of 14 chemotherapy drugs, including 5-fluorouracil and oxaliplatin. Of the 60 miRNAs, 28 were associated with chemosensitivity, 20 with chemoresistance, and one with differential expression and radiosensitivity; ten miRNAs were not associated with any impact on chemotherapy. The results outline the importance of 34 drug–regulatory pathways of chemoresistance and sensitivity in CRC. The mean effect size was 0.689 (95% confidence interval 0.428–1.110), indicating that the expression of miRNAs decreased the likelihood of death by about 32%.


Studies have consistently shown that multiple miRNAs could act as clinical predictors of chemoresistance and sensitivity. An inclusion of supplementary miRNA estimation in CRC routine practice needs to be considered to evaluate the efficacy of chemotherapy after confirming our findings with large-scale prospective cohort studies.

PROSPERO registration number




The authors acknowledge the Meta-analysis Concepts and Applications workshop manual by Michael Borenstein for his guidelines on reporting meta-analysis, subgroup analysis and publication bias, (

Author Contributions

RJ contributed to the conceptualisation, study design, search strategy, protocol development, and review by revising different versions. RJ, MRM, CK, SB, AG, NR and KMG provided input into the study design, supervision, ensured the absence of errors, and arbitrated in case of disagreement. MRM and CK engaged in initial searches to determine the feasibility and in the data collection, analysis, and drafting of the manuscript. All authors read and approved the final version of the manuscript.

Compliance with Ethical Standards


No sources of funding were used to conduct this study or prepare this manuscript.

Conflict of interest

RJ, MRM, CK, SB, AG, NR and KMG have no conflicts of interest that are directly relevant to the content of this article.

Supplementary material

40291_2019_381_MOESM1_ESM.tif (98 kb)
Supplementary material 1 (TIFF 97 kb)
40291_2019_381_MOESM2_ESM.tif (122 kb)
Supplementary material 2 (TIFF 121 kb)


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Biotechnology, School of Bio-Sciences and TechnologyVellore Institute of Technology (VIT)VelloreIndia
  2. 2.North Terrace Campus, University of AdelaideAdelaideAustralia
  3. 3.Department of Clinical Sciences, College of Health and Human Sciences, Yellow 1.1.05Charles Darwin UniversityDarwinAustralia
  4. 4.Genesis Cancer Care CentreBunburyAustralia
  5. 5.American Oncology InstituteNagpurIndia

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