Expression of Sestrin Genes in Radiotherapy for Prostate Cancer and Its Association With Fatigue: A Proof-of-Concept Study

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Abstract
Participants completed the 13-item Functional Assessment of Cancer Therapy—Fatigue subscale, Spanish version. Whole blood samples were collected at baseline and at the midpoint of EBRT. Gene expression data were analyzed using the limma package in the R (version R 2.14.0.) statistical software. Linear models and empirical Bayes moderation, adjusted for radiation fraction (total number of days of prescribed radiation treatment), were used to examine potential associations between changes in gene expression and change in fatigue scores. Expression of SESN3 (adjusted p < .01, log fold change −0.649) was significantly downregulated during EBRT, whereas the expressions of SESN1 and SESN2 remained unchanged. After adjustment for radiation fraction, change in SESN3 expression was associated with change in fatigue during EBRT (false discovery rate <.01). Downregulation of SESN3, a novel pharmacoactive stress response gene, was associated with fatigue intensification during EBRT. SESN3 may serve as an interventional target and a biomarker for the cellular and molecular events associated with EBRT-related fatigue.
Funding Information
  • Norges Idrettshøgskole (P30 CA168524 and P20 GM103418R01 GM28157, U19 GM61)

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