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

Velda J. Gonzalez, Farnoosh Abbas-Aghababazadeh, Brooke L. Fridley, Tomar Ghansah, Leorey N. Saligan

Research output: Contribution to journalArticlepeer-review


Genetic factors that influence inflammation and energy production/expenditure in cells may affect patient outcomes following treatment with external beam radiation therapy (EBRT). Sestrins, stress-inducible genes with antioxidant properties, have recently been implicated in several behaviors including fatigue. This proof-of-concept study explored whether the sestrin family of genes (SESN1, SESN2, and SESN3) were differentially expressed from baseline to the midpoint of EBRT in a sample of 26 Puerto Rican men with nonmetastatic prostate cancer. We also examined whether changes in expression of these genes were associated with changes in fatigue scores during EBRT. Method: 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. Results: 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)218-226
Number of pages9
JournalBiological Research for Nursing
Issue number2
StatePublished - Mar 1 2018


  • Puerto Ricans
  • SESN3
  • fatigue
  • gene expression
  • prostate cancer
  • radiotherapy
  • sestrins
  • Prostatic Neoplasms/genetics
  • Fatigue/etiology
  • Humans
  • Middle Aged
  • Gene Expression Regulation, Neoplastic
  • Male
  • Hispanic or Latino
  • Bayes Theorem
  • Radiotherapy/adverse effects
  • Aged
  • Heat-Shock Proteins/genetics

ASJC Scopus subject areas

  • Research and Theory


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