RT Journal Article
SR Electronic
T1 Gene profiles of thymidine de novo and salvage pathways in 136 patients raises question of using FLT for imaging prostate cancer
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1448
OP 1448
VO 56
IS supplement 3
A1 Xiaofei Wang
A1 Peng Huang
A1 Shirley Yang
A1 Richard Wahl
YR 2015
UL http://jnm.snmjournals.org/content/56/supplement_3/1448.abstract
AB 1448 Objectives To assess the likelihood of FLT application in primary prostate cancer by the gene profile related to FLT uptake in primary prostate cancer tissue samples, measured by array chips (over 20,000 transcripts and variants).Methods A U133A array dataset published by YP Wang et al. (GSE8218) was used in the study. The dataset includes 136 prostate samples with documented percentages of tumor, stroma, hypertrophy, and atrophy. Since the nucleoside transporter, thymidine kinase, thymidylate synthetase, and thymidine phosphorylase are directly involved in FLT retention in cells, a stepwise linear regression model was used to search for genes that were associated with the percentage of tumor in the sample.Results SLC29A2 was positively correlated with the prostate tumor component (p<0.001). Other nucleoside transporters (SLC29A) and sodium-coupled nucleoside transporter (SLC28A) did not yield a significant association. Thymidine kinases (TK1 and 2) and thymidylate synthase (TYMS) were found to be significant (all with p<0.0035) in the model y= -52.656 + 0.186*(TK1) + 0.351*(TYMS) -0.064*(TK2) with an adjusted R square= 0.223. SLC29A2 was independently associated with the percentage of tumor (p<0.0001) after adjusting for TK1, TK2, and TYMS. The regression model with these 4 variables included increased an adjusted R square to 0.33.Conclusions 33% of the variation in the percentage tumor in these prostate samples was predicted by nucleoside transporters, thymidine kinases and thymidylate synthase, suggesting that FLT might not be an optimal probe to detect early primary prostate cancer.Research Support T32EB006351