Cancer-Related Fatigue and the Adaptive Response to Oxidative Stress

Authors

• K Dickinson
• D Wang
• J Barb
• JP Bennett
• S Collins
• D Lyon
• LN Saligan

Abstract

Background: Approximately 70% of men report clinically-significant fatigue while receiving external beam radiation therapy (EBRT) for non-metastatic prostate cancer (NM-PC). Objective: To understand the biologic underpinning of fatigue by comparing the differential expression of cellular stress response genes related to EBRT between fatigued and non-fatigued participants. Methods: 35 participants were enrolled in an IRB-approved study. Fatigue, as assessed by the Functional Assessment of Cancer Therapy–Fatigue subscale (FACT-F) and peripheral blood were obtained at Day 1 (T2) and completion (T6) of EBRT. Participants were grouped into high (HF) and no fatigue (NF) groups based on change in FACT-F scores from T2 to T6. Differential expression of genes related to apoptosis, autophagy, and necrosis were assessed by qPCR. Results: There were no significant differences in gene expression between the fatigue groups at T2 or T6. However, there were differentially expressed genes within each group over time. Three genes were significantly different from T1 to T6 in the HF group, CD70 (p=0.04), FAF1 (p=0.002), and GALNT5 (p=0.03). Discussion: Apoptosis-inducing gene CD70 and TNF-inducing necrosis gene GALNT5 were upregulated, while the pro-apoptosis gene FAF1 was downregulated in the HF group. These results imply that apoptosis may influence the fatigue experience and the apoptosis may result from a more immune-mediated pathway involving CD70 expression. Conclusions: These results imply that inflammatory-mediated apoptotic response to oxidative stress may influence the fatigue experience of men receiving EBRT for NM-PC. Understanding the etiology of radiation-related fatigue has significant clinical implications for personalizing cancer therapy and prospectively attenuating symptoms.

Scientific Focus Area: Social and Behavioral Sciences

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