%0 Journal Article
%T Analysis of the mRNA Expression of Chemotherapy-Related Genes in Colorectal Carcinoma Using the Danenberg Tumor Profile Method
%A Shin Sasaki
%A Toshiyuki Watanabe
%A Hiroshi Nakayama
%J Journal of Oncology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/386906
%X The establishment of individualized chemotherapy for colorectal carcinoma based on the expression of genes involved in chemotherapeutic sensitivity or prognosis is necessary. To achieve this, the expression profiles of genes within tumors and their relationship to clinicopathological factors must be elucidated. Here, we selected 10 genes (TS, DPD, TP, FPGS, GGH, DHFR, ERCC1, TOPO-1, VEGF, and EGFR), examined differences in their mRNA expression between the upper and lower thirds of tumors by laser-captured microdissection and real-time RT-PCR (the Danenberg tumor profile), and analyzed the relationships between their expression profiles and clinicopathological factors. Interestingly, the mRNA expression of DPD, TP, and VEGF was significantly higher in the lower third than in the upper third of tumors ( , , and , resp.). Furthermore, increased ERCC1 mRNA expression in the lower third of tumors correlated with recurrence ( ), and VEGF mRNA expression was significantly higher in cases with recurrence than in cases without recurrence, both in the upper and lower thirds of tumors ( and , resp.). These results implied that heterogeneity in DPD, TP, and VEGF expression may exist in colorectal carcinoma and that ERCC-1 and VEGF may be markers predicting recurrence after curative operation. 1. Introduction 5-Fluorouracil (5-FU) and its relatives are mainstays in the chemotherapeutic treatment of colorectal carcinoma [1, 2]. Recently, several newly discovered drugs, including molecular targeted agents, have facilitated the progression and diversifications of chemotherapies. Furthermore, many studies have reported that a variety of candidates can be used to predict chemotherapeutic sensitivity or prognosis [3], and the establishment of individualized chemotherapy based on the expression profiles of these genes is necessary for promoting the efficacy of chemotherapeutic agents in both nonresponders and responders. To achieve this, differences in gene expression profiles and distributions throughout the tumor must be analyzed, and relationships between the distribution and extent of gene expression and clinicopathological factors must be elucidated. Among the many candidates reported thus far, we selected 10 genes that have been extensively analyzed as possible factors related to chemosensitivity and/or prognosis in colorectal carcinoma. Six genes (thymidylate synthetase TS, dihydropyrimidine dehydrogenase DPD, thymidine phosphorylase TP, folylpolyglutamate synthetase FPGS, gamma-glutamyl hydrolase GGH, and dihydrofolate reductase DHFR) are known to be involved in
%U http://www.hindawi.com/journals/jo/2013/386906/