Analysis of the mRNA expression of chemotherapy-related genes in colorectal carcinoma using the danenberg tumor profile method.

Abstract

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 (P = 0.044, 0.023, and 0.013, resp.). Furthermore, increased ERCC1 mRNA expression in the lower third of tumors correlated with recurrence (P = 0.049), 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 (P = 0.018 and 0.036, 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.