Gene Expression, and Fatigue in Puerto Rican Men during Radiotherapy for Prostate Cancer: an Exploratory Study

Abstract

Objective: To examine the trajectory of fatigue experienced by 26 Puerto Rican (PR) men over the course of External Beam Radiation Therapy (EBRT) and to assess gene expression changes from baseline to midpoint of EBRT using microarray technology. Design/Research Approach- Prospective exploratory and comparative design study. Setting- RT facility located in San Juan, PR. Sample/Participants-26 PR men with non-metastatic prostate cancer. Methods: Participants completed 2 paper forms: demographics and the Spanish version of the 13-item FACT–fatigue at baseline, midpoint, and end of EBRT. Wholeblood samples were collected at baseline and at midpoint of EBRT. Descriptive data was analyzed using t-test, Wilcoxon, and Friedman test for repeated measures. Gene expression data was analyzed using the LIMMA package in R; the functional network analysis was conducted using Ingenuity Pathway analysis. Main Research Variable-Fatigue scores, gene expression. Results: Subjects were of ages 52-81 with fatigue scores that remained unchanged during EBRT (baseline=42.38, SD=9.34; midpoint=42.11, SD=8.93, endpoint=43.04, SD=8.62). Three hundred seventy-three genes (130-up regulated and 243-down regulated) were differentially expressed from baseline to mid-point of EBRT (FDR<0.01). The top distinct canonical pathways of the differentially expressed probesets (p<0.0001) were: “Phospholipase C Signaling,” “Role of NFAT in Regulation of the Immune Response,” and “Gαq Signaling.” Conclusion: While fatigue did not worsen over the course of EBRT for this sample as a group, there was variability in fatigue across the sample. It is possible that the over expression of the SESN3 gene, known to suppress oxidative damage, may have contributed to the attenuation of fatigue in this clinical population.