MicroRNAs as diagnostic and prognostic biomarkers in chemotherapy-induced peripheral neuropathy: A systematic review

Table 4 Qualitative assessment of clinical and methodological heterogeneity across included studies

Ref.	Cancer type	Neurotoxic agent	Study design	CIPN definition/grading	Sample source	miRNA platform	Timing of sampling	Key source of heterogeneity
Davey et al[36], 2023	Breast cancer	Paclitaxel	Prospective cohort	NCI-CTCAE (grade not stratified)	Whole blood	qRT-PCR (predefined panel)	During chemotherapy	Whole blood vs plasma/serum; limited miRNA panel
Ju et al[37], 2022	Gastric cancer	Oxaliplatin (XELOX)	Prospective cohort	NCI-CTCAE; cycle-based severity	Plasma	Small RNA sequencing + qRT-PCR validation	After < 4 vs ≥ 4 cycles	Cycle-based CIPN definition; sequencing-based discovery
Ju et al[38], 2024	Colorectal cancer	Oxaliplatin (FOLFOX)	Prospective cohort	NCI-CTCAE; ≤ 3 vs ≥ 6 cycles	Plasma	RNA sequencing + qRT-PCR validation	Early vs late chemotherapy exposure	Dose/cycle-based stratification; stress biomarker integration
Łuczkowska et al[39], 2021	Multiple myeloma	Bortezomib-based regimens	Case-control	NCI-CTCAE (IMWG-adapted)	Plasma	Microarray + qRT-PCR validation	During treatment	Different malignancy and neurotoxicity mechanism
Noda-Narita et al[40], 2020	Breast cancer	Paclitaxel	Retrospective cohort	NCI-CTCAE ≥ grade 2 vs ≤ 1	Serum	Microarray	Pre-treatment	Different grade threshold and retrospective design

CIPN: Chemotherapy-induced peripheral neuropathy; miRNA: MicroRNA; NCI-CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events; RNA sequencing: RNA sequencing (typically small RNA sequencing when profiling miRNAs); qRT-PCR: Quantitative reverse transcription polymerase chain reaction; XELOX: Oxaliplatin and capecitabine; FOLFOX: 5-fluorouracil, leucovorin, and oxaliplatin; IMWG: International Myeloma Working Group.