Constitutive mRNA expression of DNA repair-related genes as a biomarker for clinical radio-resistance: A pilot study in prostate cancer patients receiving radiotherapy.
OBJECTIVE
Repair of radiation-induced DNA damage is believed to play a critical role in the development of adverse reactions in radiotherapy patients. Constitutive mRNA expression of repair genes was investigated in such patients to analyze whether expression patterns are predictive for therapy-related acute side effects.


METHODS
Prostate cancer patients (n = 406) receiving intensity-modulated radiotherapy were recruited in a prospective epidemiological study. Adverse effects were monitored during therapy using common toxicity criteria. For expression analyses, samples from 58 patients were selected according to their observed grade of clinical side effects to radiotherapy. Expression profiles were generated from peripheral blood lymphocytes using customized cDNA-arrays which carried probes for 143 DNA repair or repair-related genes. In addition, expression of selected genes was confirmed by quantitative real-time reverse transcription PCR (RT-PCR). Constitutive mRNA expression profiles were analyzed for predicting acute clinical radiosensitivity or radio-resistance.


RESULTS
Cluster analysis identified 19 differentially expressed genes. Many of these genes are involved in DNA double strand break repair. Expression levels of these genes differed up to 7-fold from the mean of all patients whereas expression levels of housekeeping genes varied only up to 2-fold. High expression of the identified genes was associated with a lack of clinical radiation sensitivity thus indicating radio-resistance.


CONCLUSIONS
Constitutive expression of DNA repair-related genes may affect the development of acute side effects in radiotherapy patients, and high expression levels of these genes seem to support protection from adverse reactions.
Hümmerich
Jörg
J
Division of Toxicology and Cancer Risk Factors, Heidelberg, Germany.
Werle-Schneider
Gisela
G
Popanda
Odilia
O
Celebi
Oktay
O
Chang-Claude
Jenny
J
Kropp
Silke
S
Mayer
Claudia
C
Debus
Jürgen
J
Bartsch
Helmut
H
Schmezer
Peter
P
D014408:Biomarkers, Tumor / Q000378:metabolism*; D004260:DNA Repair / Q000528:radiation effects*; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D010865:Pilot Projects; D011471:Prostatic Neoplasms / Q000503:physiopathology* / Q000532:radiotherapy*; D012333:RNA, Messenger / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger