Objectives MicroRNAs (miRNAs) have recently been reported as useful diagnostic markers in cancer; however, relationships of miRNAs with adverse events during chemotherapy have yet to be fully described. In this study, we examined the relationship between serum miRNA and the risk of peripheral neuropathy (PN), a common and persistent adverse event induced by paclitaxel, in patients with breast cancer.
Methods A total of 84 serum samples from patients with breast cancer, who received paclitaxel as neoadjuvant or adjuvant chemotherapy, were obtained between January 2011 and September 2013 at National Cancer Center Hospital. Samples were divided, 2:1, into a training cohort and a test cohort, respectively; both cohorts included specimens from patients with severe PN (≥grade 2, PN group) and non-severe PN controls (non-PN group). The training cohort was used to identify miRNAs, and combinations thereof, that could predict PN, which then were validated in the test cohort.
Results Eighty-four patients received paclitaxel: 38 and 46 patients in the PN and non-PN groups, respectively. We identified 15 discriminatory miRNAs with |fold change|>0.5, and 14 combinations of three miRNAs showed the ability to discriminate, with sensitivity, specificity and accuracy of >50%. The most discriminatory miRNA, with the highest |fold change|, was miR-451a, which regulates the expression of the drug-transporter protein P-glycoprotein, potentially promoting paclitaxel resistance.
Conclusion MiR-451a could be a predictive marker for PN caused by paclitaxel-containing chemotherapy; however, further investigation of the underlying mechanism is required to determine the role of miR-451a.
- peripheral neuropathy
- and breast cancer
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Contributors SN-N, AS, CS and TO conceived the study and designed the experiments. SN-N, AS, YT, CS and KT participated in the data collection. SN-N, AS, JK, ST and YA conducted the experiments. JK, JM and ST performed the statistical analysis. SN-N, AS and JM interpreted the data and wrote the manuscript. All authors have read and approved the submission of the manuscript.
Funding This study was financially supported through a 'Development of Diagnostic Technology for Detection of miRNA in Body Fluids' grant from the Japanese Agency for Medical Research and Development.
Competing interests JK and ST are employees of Toray Industries, Inc, the provider of the 3D-Gene system. YA is an employee of Dynacom Co., Ltd, the developer of the statistical script used for selecting the best miRNA combination. All the other authors have no conflict of interest to declare.
Patient consent for publication Obtained.
Ethics approval The present study involving human subjects was approved by the National Cancer Center Hospital Institutional Review Board (2016–120, G2009-005) and the Human Tissue Samples Ethics Committee for R&D, Toray Industries (HC2018-2). Written informed consent was obtained from each subject.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request.
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