Differing leukocyte gene expression profiles associated with fatigue in patients with prostate cancer versus chronic fatigue syndrome.
BACKGROUND
Androgen deprivation therapy (ADT) often worsens fatigue in patients with prostate cancer, producing symptoms similar to chronic fatigue syndrome (CFS). Comparing expression (mRNA) of many fatigue-related genes in patients with ADT-treated prostate cancer versus with CFS versus healthy controls, and correlating mRNA with fatigue severity may clarify the differing pathways underlying fatigue in these conditions.


METHODS
Quantitative real-time PCR was performed on leukocytes from 30 fatigued, ADT-treated prostate cancer patients (PCF), 39 patients with CFS and 22 controls aged 40-79, together with ratings of fatigue and pain severity. 46 genes from these pathways were included: (1) adrenergic/monoamine/neuropeptides, (2) immune, (3) metabolite-detecting, (4) mitochondrial/energy, (5) transcription factors.


RESULTS
PCF patients showed higher expression than controls or CFS of 2 immune transcription genes (NR3C1 and TLR4), chemokine CXCR4, and mitochondrial gene SOD2. They showed lower expression of 2 vasodilation-related genes (ADRB2 and VIPR2), 2 cytokines (TNF and LTA), and 2 metabolite-detecting receptors (ASIC3 and P2RX7). CFS patients showed higher P2RX7 and lower HSPA2 versus controls and PCF. Correlations with fatigue severity were similar in PCF and CFS for only DBI, the GABA-A receptor modulator (r=-0.50, p<0.005 and r=-0.34, p<0.05). Purinergic P2RY1 was correlated only with PCF fatigue and pain severity (r=+0.43 and +0.59, p=0.025 and p=0.001).


CONCLUSIONS
PCF patients differed from controls and CFS in mean expression of 10 genes from all 5 pathways. Correlations with fatigue severity implicated DBI for both patient groups and P2RY1 for PCF only. These pathways may provide new targets for interventions to reduce fatigue.
Department of Anesthesiology, University of Utah Health Sciences Center, Salt Lake City, UT, USA. Electronic address: kathleen.c.light@hsc.utah.edu.
Kathleen C
KC
Light
Neeraj
N
Agarwal
Eli
E
Iacob
Andrea T
AT
White
Anita Y
AY
Kinney
Timothy A
TA
VanHaitsma
Hannah
H
Aizad
Ronald W
RW
Hughen
Lucinda
L
Bateman
Alan R
AR
Light
D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003863:Depression / Q000523:psychology; D015444:Exercise / Q000502:physiology; D005221:Fatigue / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D015673:Fatigue Syndrome, Chronic / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000523:psychology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012044:Regression Analysis; D012890:Sleep / Q000502:physiology
D018076:DNA, Complementary; D012333:RNA, Messenger
Chronic fatigue syndrome; Cytokine; Fatigue; GABA-receptor modulator; Gene expression; Prostate cancer; Purinergic; qPCR