BACKGROUND: To identify a molecular marker associated with volumetric changes to radiotherapy (RT) in cervical cancer, we compared gene expression profiles of an early response (ER) group with a late response (LR) group, which are defined by complete and partial disappearance of a primary cervical lesion on MRI performed 1 month after completion of RT. METHODS: Microarray analysis of mRNA expression profiles was performed in 17 patients (11 in the ER and 6 in the LR group). After selection of the genes with significant differential expression, we evaluated the association of the selected genes with radioresistance in clinical specimens. RESULTS: We identified 53 genes with differential expression on microarray analysis using the permutation test with t statistics (p ≤ 0.01). Using immunohistochemistry, we evaluated the expression of RAR-β, one of the genes selected among the differentially expressed genes. RAR-β expression was significantly down-regulated in the LR group compared with the ER group (p = 0.02). However, this gene did not predict permanent radioresistance (p = 0.19). CONCLUSIONS: RAR-β expression might be a valuable marker for the prediction of early volumetric changes to RT in cervical carcinomas. Further search for additional genes associated with early volumetric changes and radioresistance may aid in refining individual treatment strategies.
BACKGROUND: To identify a molecular marker associated with volumetric changes to radiotherapy (RT) in cervical cancer, we compared gene expression profiles of an early response (ER) group with a late response (LR) group, which are defined by complete and partial disappearance of a primary cervical lesion on MRI performed 1 month after completion of RT. METHODS: Microarray analysis of mRNA expression profiles was performed in 17 patients (11 in the ER and 6 in the LR group). After selection of the genes with significant differential expression, we evaluated the association of the selected genes with radioresistance in clinical specimens. RESULTS: We identified 53 genes with differential expression on microarray analysis using the permutation test with t statistics (p ≤ 0.01). Using immunohistochemistry, we evaluated the expression of RAR-β, one of the genes selected among the differentially expressed genes. RAR-β expression was significantly down-regulated in the LR group compared with the ER group (p = 0.02). However, this gene did not predict permanent radioresistance (p = 0.19). CONCLUSIONS: RAR-β expression might be a valuable marker for the prediction of early volumetric changes to RT in cervical carcinomas. Further search for additional genes associated with early volumetric changes and radioresistance may aid in refining individual treatment strategies.
Authors: Rob Noorlag; Pauline M W van Kempen; Cathy B Moelans; Rick de Jong; Laura E R Blok; Ronald Koole; Wilko Grolman; Paul J van Diest; Robert J J van Es; Stefan M Willems Journal: Epigenetics Date: 2014-07-08 Impact factor: 4.528