Plasma miR-98-5p as a candidate biomarker of pain severity in oxaliplatin-induced peripheral neuropathy related to NGF and catecholamine dysregulation.

BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) is a common and severe adverse event in patients with gastrointestinal (GI) cancer who undergo oxaliplatin-based chemotherapy. Assessments remain largely dependent on a numeric rating scale (NRS), which is needed for early detection and objective quantification of pain intensity. METHODS: This study aimed to identify differentially expressed microRNAs (miRNAs) in plasma samples from 22 patients with GI cancer treated with oxaliplatin to elucidate the association between candidate miRNA expression levels, nerve growth factor (NGF), catecholamines, and NRS scores for peripheral neuropathic pain. High-throughput RNA sequencing was used to analyze miRNA expression profiles, and patients were stratified into Groups 1 (n = 10, no or mild pain) and 2 (n = 12, moderate or severe pain) based on their NRS scores. Correlations between variables were assessed using Spearman's rank-order correlation (r = 0.4031, P = 0.0629). RESULTS: In Group 2, hsa-miR-98-5p was significantly upregulated and demonstrated the greatest potential to stratify patients by pain severity among the candidate miRNAs (The area under the curve = 0.8083, 95% CI: 0.6222-0.9944). Gene ontology enrichment analysis revealed that hsa-miR-98-5p was significantly associated with critical neuronal injury and repair signaling pathways. Patients in Group 2 exhibited decreased norepinephrine and dopamine levels, elevated NGF levels, and elevated cortisol levels, indicating potential alterations in the OIPN neuromodulatory systems. CONCLUSION: These findings suggest that miR-98-5p is a candidate biomarker of pain severity in OIPN and may play a role in OIPN pathophysiology.