PURPOSE: Radiation therapy (RT) and androgen deprivation therapy (ADT) impair muscular, mitochondrial and immune function, and result in weakness and cancer-related fatigue (CRF) among prostate cancer patients. We investigated the influence of an exercise intervention (EXCAP©®), including resistance and aerobic training, on expression of 4825 mitochondrial and nuclear genes, muscular strength, and CRF.
METHODS: In this phase II randomized clinical trial, prostate cancer patients (N=58; mean age=67), receiving RT (47%) or ADT (53%), were randomized to 6 wks of EXCAP©® (7 days/wk) or standard care (RT or ADT with no exercise). RNA was isolated from muscle biopsies for microarray analyses of 4825 mitochondrial and nuclear genes. Muscular strength was assessed using multiple repetition maximum testing (chest press and leg extension). CRF was assessed via valid self-report questionnaires (BFI, MFSI). Assessments were pre- and post-intervention. Analyses included robust multi-array average normalization, analyses of covariance (ANCOVA), correlations and partial least squares (PLS) with cross-validation.
RESULTS: Analyses revealed >2-fold down regulation in MYH8 and XIRP1 in the exercise group, no >2-fold changes in expression in the control group, and a >2-fold difference between groups on MTTM where MTTM was down-regulated >1.5-fold in controls with no change in exercisers (all p<0.05). ANCOVAs revealed a trend for group differences in muscular strength (all p<0.10) with significant group differences in CRF on the BFI (p<0.05) and a trend on the MFSI (p<0.10): exercisers improved while controls worsened. MYH8, MYL5, ACTN3, XIRP1, MTTM, and HLA-DQB1 were significantly correlated with muscular strength and CRF (all p<0.05). PLS suggested down-regulation of MYL5, ACTN3, and HLA-DQB1 may optimally predict increases in CRF.
CONCLUSIONS: Results suggest exercise alters gene expression, muscular strength and CRF in prostate cancer patients. Expression changes in genes that are involved in muscle atrophy and inflammatory myopathies are related to and may mediate the relationship between exercise and CRF. Future research is needed to confirm these findings in larger phase III clinical trials. ClinicalTrials.Gov: NCT00815672 Funding: DOD W81XWH-07-1-0341
