TY - JOUR
T1 - Variance in the expression of 5-fluorouracil pathway genes in colorectal cancer
AU - Kidd, Elizabeth A.
AU - Yu, Jinsheng
AU - Li, Xia
AU - Shannon, William D.
AU - Watson, Mark A.
AU - McLeod, Howard L.
PY - 2005/4/1
Y1 - 2005/4/1
N2 - Although colorectal cancer has the third highest cancer mortality rate, the treatment remains far from optimized with patients showing variable responses to standard treatment. Molecular differences in pharmacologically relevant genes may contribute to the variability in response. This study used Taqman PCR to investigate the expression of 24 5-fluorouracil (5-FU) pathway genes in colorectal cancer using paired nontumor and tumor sample from 52 patients with Dukes' C colon cancer. In comparing tumor versus nonmalignant tissue, 14 of the 24 genes showed significant variation in gene expression. For 11 of these same genes (FPGS, DHFR, GGH, NME1, NME2, RRM2, UMPH2, UNG, UMPS, TP53, and TK1), a significant proportion of the patients showed an over expression of the particular gene in tumor tissue with a tumor-to-nonmalignant (T/N) ratio >1.2, whereas one gene (DPYD) showed the converse with a large number of patients showing a lower expression in the tumor tissue (T/N < 0.8). Multiple gene correlations for the genes of the 5-FU pathway were found with the Spearman rank correlation of >0.6 (all P > 0.001), suggesting possible coregulation mechanisms. Hierarchical clustering analysis created at least three groups of genes, which were consistent with groupings by the other statistical methods. Additionally, the hierarchical clustering showed two distinct groups of patients based on their gene expression. These variations in gene expression could provide valuable insights for optimizing treatment selection for patients with colorectal cancer.
AB - Although colorectal cancer has the third highest cancer mortality rate, the treatment remains far from optimized with patients showing variable responses to standard treatment. Molecular differences in pharmacologically relevant genes may contribute to the variability in response. This study used Taqman PCR to investigate the expression of 24 5-fluorouracil (5-FU) pathway genes in colorectal cancer using paired nontumor and tumor sample from 52 patients with Dukes' C colon cancer. In comparing tumor versus nonmalignant tissue, 14 of the 24 genes showed significant variation in gene expression. For 11 of these same genes (FPGS, DHFR, GGH, NME1, NME2, RRM2, UMPH2, UNG, UMPS, TP53, and TK1), a significant proportion of the patients showed an over expression of the particular gene in tumor tissue with a tumor-to-nonmalignant (T/N) ratio >1.2, whereas one gene (DPYD) showed the converse with a large number of patients showing a lower expression in the tumor tissue (T/N < 0.8). Multiple gene correlations for the genes of the 5-FU pathway were found with the Spearman rank correlation of >0.6 (all P > 0.001), suggesting possible coregulation mechanisms. Hierarchical clustering analysis created at least three groups of genes, which were consistent with groupings by the other statistical methods. Additionally, the hierarchical clustering showed two distinct groups of patients based on their gene expression. These variations in gene expression could provide valuable insights for optimizing treatment selection for patients with colorectal cancer.
UR - http://www.scopus.com/inward/record.url?scp=17644373059&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-04-1258
DO - 10.1158/1078-0432.CCR-04-1258
M3 - Article
C2 - 15814641
AN - SCOPUS:17644373059
SN - 1078-0432
VL - 11
SP - 2612
EP - 2619
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 7
ER -