mGluR5 mediates post-radiotherapy fatigue development in cancer patients

Translational Psychiatry
Li Rebekah FengLeorey N Saligan

Abstract

Cancer-related fatigue (CRF) is a common burden in cancer patients and little is known about its underlying mechanism. The primary aim of this study was to identify gene signatures predictive of post-radiotherapy fatigue in prostate cancer patients. We employed Fisher Linear Discriminant Analysis (LDA) to identify predictive genes using whole genome microarray data from 36 men with prostate cancer. Ingenuity Pathway Analysis was used to determine functional networks of the predictive genes. Functional validation was performed using a T lymphocyte cell line, Jurkat E6.1. Cells were pretreated with metabotropic glutamate receptor 5 (mGluR5) agonist (DHPG), antagonist (MPEP), or control (PBS) for 20 min before irradiation at 8 Gy in a Mark-1 γ-irradiator. NF-κB activation was assessed using a NF-κB/Jurkat/GFP Transcriptional Reporter Cell Line. LDA achieved 83.3% accuracy in predicting post-radiotherapy fatigue. "Glutamate receptor signaling" was the most significant (p = 0.0002) pathway among the predictive genes. Functional validation using Jurkat cells revealed clustering of mGluR5 receptors as well as increased regulated on activation, normal T cell expressed and secreted (RANTES) production post irradiation in cells pretreate...Continue Reading

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Citations

Oct 31, 2018·Journal of Nursing Scholarship : an Official Publication of Sigma Theta Tau International Honor Society of Nursing·Leorey N Saligan
May 30, 2019·Expert Opinion on Drug Discovery·Óscar Álvarez-Machancoses, Juan Luis Fernández-Martínez
Aug 14, 2019·Cancer Medicine·Li Rebekah FengLeorey N Saligan
May 23, 2020·International Journal of Molecular Sciences·Juan Luis Fernández-MartínezAndrzej Kloczkowski
Oct 8, 2019·Journal of Medical Imaging and Radiation Oncology·Vindya BandaraJarad Martin
Aug 27, 2019·Frontiers in Immunology·Mark R ZielinskiNoel R Rose
Feb 4, 2021·Cancer Medicine·Li Rebekah FengLeorey N Saligan
Jul 4, 2020·Reports of Practical Oncology and Radiotherapy : Journal of Greatpoland Cancer Center in Poznań and Polish Society of Radiation Oncology·Sarkar Siddique, James C L Chow
Jun 4, 2021·Frontiers in Cell and Developmental Biology·Li Rebekah FengLeorey Saligan
Jan 10, 2019·Oncology·Li Rebekah FengLeorey N Saligan

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Datasets Mentioned

BETA
GSE30174

Methods Mentioned

BETA
chips
PCR
electrophoresis
Confocal microscopy
nuclear translocation

Clinical Trials Mentioned

NCT00852111

Software Mentioned

Partek Genomics Suite
SPSS
Affymetrix GeneChip Command Console
Ingenuity Pathway Analysis ( IPA

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