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MicroRNAs as diagnostic and prognostic biomarkers in chemotherapy-induced peripheral neuropathy: A systematic review
Tsampika-Vasileia Kalamara, Dimitrios A Andreikos, Konstantinos Dodos, Elisavet Georgiou, George Fotakopoulos, Nikolaos Foroglou, Dorothea Kapoukranidou, Vasiliki E Georgakopoulou
Tsampika-Vasileia Kalamara, Konstantinos Dodos, Dorothea Kapoukranidou, Laboratory of Physiology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Kentrikí Makedonía, Greece
Dimitrios A Andreikos, School of Medicine, Democritus University of Thrace, Alexandroupoli 68100, Anatolikí Makedonía kai Thráki, Greece
Elisavet Georgiou, Laboratory of Biological Chemistry, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Kentrikí Makedonía, Greece
George Fotakopoulos, Nikolaos Foroglou, Department of Neurosurgery, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki 54636, Kentrikí Makedonía, Greece
Vasiliki E Georgakopoulou, Department of Pathophysiology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens 11527, Greece
Co-first authors: Tsampika-Vasileia Kalamara and Dimitrios A Andreikos.
Author contributions: Georgakopoulou VE performed the research and analyzed the data and wrote the manuscript; Kalamara TV and Andreikos DA drafted substantial parts of the manuscript, performed the systematic literature search, participated in study selection (titles/abstracts and full texts), extracted, organized and verified data, contributed to the preparation of tables and figures; contributed to data interpretation; and assisted in its critical revision, and they contributed equally to this manuscript as co-first authors; Kalamara TV, Andreikos DA, Dodos K, and Georgakopoulou VE contributed to the design of the study; Dodos K, contributed to methodology; assisted in data extraction and synthesis, critical appraisal of included studies, participated in drafting and revising the methods and discussion sections; Georgiou E contributed to the interpretation of preclinical and translational data, critically reviewed the manuscript for scientific accuracy and coherence; Fotakopoulos G and Kapoukranidou D critically revised the manuscript for important intellectual content; Fotakopoulos G provided clinical expertise in neuro-oncology and chemotherapy-induced peripheral neuropathy, contributed to the interpretation of the clinical relevance of findings; Foroglou N provided neurosurgical and clinical oncology input, contributed to the interpretation of clinical implications and potential translational applications; Kapoukranidou D provided expertise in physiology and neurobiology, contributed to the interpretation of mechanistic aspects of microRNA involvement in chemotherapy-induced peripheral neuropathy. All authors have read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Vasiliki E Georgakopoulou, MD, PhD, Department of Pathophysiology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, 17 Agiou Toma Street, Athens 11527, Greece.
vaso_georgakopoulou@hotmail.com
Received: December 8, 2025
Revised: December 26, 2025
Accepted: March 20, 2026
Published online: April 24, 2026
Processing time: 134 Days and 20.4 Hours
BACKGROUND
Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent, dose-limiting toxicity of neurotoxic antineoplastic agents, yet clinicians lack minimally invasive biomarkers to predict susceptibility, monitor neuroaxonal injury and stratify long-term risk. Circulating microRNAs (miRNAs) are attractive candidates because they integrate stress and injury responses and can be robustly quantified in blood.
AIM
To systematically review human studies evaluating miRNAs as diagnostic or prognostic biomarkers of CIPN.
METHODS
Following PRISMA guidelines, we searched PubMed, Cochrane Library, Scopus and conference proceedings from inception to August 2025 for observational studies including patients with malignant disease treated with neurotoxic chemotherapy, comparing those who developed CIPN with those who did not, and reporting differences in miRNA expression. Data on clinical setting, chemotherapy type, CIPN assessment, miRNA source and quantification methods, and direction of expression changes were extracted. Owing to clinical and methodological heterogeneity, we performed a qualitative synthesis.
RESULTS
Five studies (three prospective cohorts, one case-control, one retrospective) comprising 304 patients (137 with CIPN) were included. Malignancies included breast, gastric and colorectal cancer and multiple myeloma; neurotoxic regimens involved oxaliplatin, paclitaxel and bortezomib. Across studies, 30 unique miRNAs were investigated. In multiple myeloma, miR-191-5p, miR-23a-3p, miR-24-3p, miR-92 and miR-22-3p were upregulated in patients with CIPN, with miR-22-3p showing one of the largest expression differences. In oxaliplatin-treated gastric and colorectal cancer, hsa-miR-378f, hsa-miR-885-5p, hsa-miR-200c-3p, hsa-miR-4666a-3p and miR-3184-5p were downregulated and some correlated with CIPN severity, whereas 21 miRNAs showed no significant differences and paclitaxel-based studies reported no consistent miRNA-CIPN associations.
CONCLUSION
Current human data support the biological plausibility of circulating miRNAs - particularly miR-22-3p, hsa-miR-378f and miR-3184-5p - as candidate diagnostic and prognostic biomarkers for CIPN, but the evidence base remains small and heterogeneous. Standardized, adequately powered, longitudinal studies with harmonized CIPN phenotyping, assay platforms and reporting of effect sizes and predictive accuracy are required before miRNA-based tests can be translated into routine risk stratification and monitoring of CIPN.
Core Tip: This systematic review synthesizes, for the first time, the human evidence on miRNAs as minimally invasive biomarkers of chemotherapy-induced peripheral neuropathy. Across five observational studies, 30 circulating miRNAs were profiled, with a small subset (notably miR-22-3p, hsa-miR-378f and miR-3184-5p) showing differential expression in patients with CIPN. However, inconsistent signals across cancer types and regimens, together with limited sample sizes and heterogeneous methodologies, currently preclude clinical application. The review maps the most promising candidate miRNAs and delineates key design and reporting priorities needed to move miRNA-based CIPN diagnostics and prognostics towards clinical utility.
