Exploratory identification of candidate biomarkers and molecular contributors to paclitaxel-induced peripheral neuropathy in patients with breast cancer through proteomic analysis.

BACKGROUND

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant adverse effect of paclitaxel in patients with breast cancer. However, reliable biomarkers for early detection and monitoring of CIPN are lacking.

METHODS

We investigated neurofilament light chain (NfL) and galectin-3 as candidate biomarkers for CIPN, and performed proteomic analysis to identify novel molecular contributors in two cohorts of patients with breast cancer undergoing paclitaxel therapy. Blood samples were collected longitudinally to measure NfL and galectin-3 levels. Differentially expressed proteins associated with CIPN onset were identified by proteomics.

RESULTS

NfL levels significantly increased in patients with CIPN, from as early as 3 weeks after treatment initiation. NfL levels were markedly higher in patients with vs. without CIPN. There were no changes or between-group differences in galectin-3 levels. Proteomic analysis identified upregulation of alcohol dehydrogenase 4 (ADH4) and downregulation of vesicular overexpressed in cancer prosurvival protein 1 (VOPP1) in CIPN, implicating oxidative stress and disrupted mitochondrial dynamics in the pathogenesis of CIPN.

CONCLUSION

NfL represents a candidate biomarker for early detection of CIPN, and we identified proteins potentially associated with the development of CIPN. Our findings provide further insights into the pathogenesis of CIPN. Integrating biomarkers and proteomics paves the way for precision medicine to manage chemotherapy-induced toxicities.