Journal Article

Identifying Predictors of Taxane-Induced Peripheral Neuropathy Using Mass Spectrometry-Based Proteomics Technology

Trivedi, Meghna, Chen, Emily I., Awad, Danielle, Kalinsky, Kevin, Kim Kim, Jenny, Koller, Antonius, Crew, Katherine D., Patel, Purvi, Hershman, Dawn L., Maurer, Mathew

2015

Overview

Major advances in early detection and therapy have significantly increased the survival of breast cancer patients. Unfortunately, most cancer therapies are known to carry a substantial risk of adverse long-term treatment-related effects. Little is known about patient susceptibility to severe side effects after chemotherapy. Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of taxanes. Recent advances in genome-wide genotyping and sequencing technologies have supported the discoveries of a number of pharmacogenetic markers that predict response to chemotherapy. However, effectively implementing these pharmacogenetic markers in the clinic remains a major challenge. On the other hand, recent advances in proteomic technologies incorporating mass spectrometry (MS) for biomarker discovery show great promise to provide clinically relevant protein biomarkers. In this study, we evaluated the association between protein content in serum exosomes and severity of CIPN. Women with early stage breast cancer receiving adjuvant taxane chemotherapy were assessed with the FACT-Ntx score and serum was collected before and after the taxane treatment. Based on the change in FACT-Ntx score from baseline to 12 month follow-up, we separated patients into two groups: those who had no change (Group 1, N = 9) and those who had a ≥20% worsening (Group 1, N = 8). MS-based proteomics technology was used to identify proteins present in serum exosomes to determine potential biomarkers. Mann-Whitney-Wilcoxon analysis was applied and maximum FDR was controlled at 20%. From the serum exosomes derived from this cohort, we identified over 700 proteins known to be in different subcellular locations and have different functions. Statistical analysis revealed a 12-protein signature that resulted in a distinct separation between baseline serum samples of both groups (q<0.2) suggesting that the baseline samples can predict subsequent neurotoxicity. These toxicity-associated biomarkers can be further validated in larger retrospective cohorts for their utility in identifying patients at high risk for CIPN.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Antineoplastic Agents - adverse effects / Biomarkers / Biomarkers, Tumor - blood / Breast cancer / Breast Neoplasms - blood / Breast Neoplasms - drug therapy / Bridged-Ring Compounds - adverse effects / Cancer / Cancer therapies / Care and treatment / Case-Control Studies / Chemotherapy / Chemotherapy, Adjuvant / Cohort Studies / Cytokines / Diagnosis / Epidemiology / Exosomes / Exosomes - metabolism / Female / Gene sequencing / Genomes / Genotyping / Health aspects / Humans / Mass spectrometry / Mass spectroscopy / Medicine / Middle Aged / Neoplasm Proteins - blood / Neurotoxicity / Pain / Patients / Peripheral Nervous System Diseases - blood / Peripheral Nervous System Diseases - chemically induced / Peripheral neuropathy / Pharmacology / Physicians / Polyneuropathies / Prospective Studies / Proteins / Proteomics / Proteomics - methods / Risk Factors / Scientific imaging / Side effects / Spectroscopy / Statistical analysis / Statistical methods / Stem cells / Studies / Tandem Mass Spectrometry / Taxane / Taxanes / Taxoids - adverse effects / Technology / Toxicity / Womens health