Identification of Genes that Predict Lymph Node Metastasis in Colorectal Cancer Cases

Currently, Endoscopic mucosal resection (EMR) and laparoscopic surgery with colorectal cancer (CRC) and has been expanding rapidly. In handling of colon cancer, adaptation of EMR is determined by the depth of tumor invasion. It is important to identify genes to predict lymph node metastasis in early CRC tumors precisely in a reproducible fashion to determine the adaptation of EMR treatment. We performed the comprehensive analysis of gene expression and genomic copy number simultaneously in CRC primary tumors to identify the bona-fide indicator of lymph node metastasis.We collected cancer cells specifically by Laser Microdissection (LMD) on 157 cases of primary colorectal cancer, and performed oligo microarrays for gene expression (GE) and aCGH for copy number aberration. As for candidate genes to be associated with lymph node metastasis, we examined reprodicibility by quantitative RT-PCR using cDNA created from the RNA extracted from 172 cases of CRC.As for the association of lymph node metastasis, we found that 240 genes and 54 genes by aCGH and by oligo GE microarray, respectively. According to database of those two arrays, 501 genes were significantly correlated (correlation coefficient > 0.7) with each other, and we found that 11 out of 501 genes were identified as lymph node metastasis related genes with copy number alteration. Of these 11 genes, we focused on PCM1, MTUS1, ASAH1 on 8p22. Then, we confirmed that the decreased expression and genomic deletion of MTUS1 were observed in lymph node positive cases (p = 0.0195) in another subset of 172 cases of CRC.To measure the expression of MTUS1 of the tumor by PCR, we can predict the presence of lymph node metastasis. We expected that the loss of MTUS1 should be an important marker in determining the adaptation of endoscopic resection.