Abstract 1739: Is there a relationship between mRNA expression levels of cancer progression related genes with prognosis in colorectal cancer patients
Authors: Miriam E. Uhlmann, Martin Sill, Ulrich Linnemann, Martin R. Berger
Journal: Cancer Research (2010)

Abstract Colorectal cancer (CRC) is correlated with genetic alterations including decreased expression of tumor suppressor genes and increased activity of oncogenes. In addition to those with well established importance, a series of new genes has been identified with regard to certain properties which cancers acquire in order to progress into more malignant neoplasias. We hypothesized that the expression levels of these genes might be related to UICC staging and clinical outcome of CRC patients. To test this hypothesis, tumor samples from 118 colorectal cancer patients were screened retrospectively by qRT-PCR for expression of the four tumor progression associated genes osteopontin (OPN), transforming growth factor β (TGF-β), matrix metalloprotease 2 (MMP2), and cyclooxigenase 2 (Cox2). The cohort consisted of 51 male and 67 female patients with a mean age of 66 years. They had been surgically treated between 1/1999 and 7/2001 in the municipal hospital of Nuernberg (Germany) and were assigned to UICC stages by pathological routine examination (I, n=20; II, n= 44; III n= 34; IV, n= 20). The resulting qRT-PCR values were compared after relating the gene expression levels of the four genes in tumor tissue to those of housekeeping genes and those obtained from normal mucosa, respectively. The patients were clustered for similar expression levels between the four genes with R statistical software using the package pvclust which provides bootstrap agglomerative hierarchical clustering to estimate the stability of resulting clusters with according p-values. Clusters with similar expression of the four genes were analyzed for correlation with known parameters of prognosis (UICC stages, mean survival time). The expression of the four genes varied considerably within the cohort of patients investigated. The highest median level was found for Cox2 (4.2) followed by MMP2 (1.8), OPN (0.73), and TGF-β (0.34). There was no obvious relation to tumor staging. Cluster analysis of the genes showed that TGF-β was most related to MMP2, followed by OPN and Cox2. Further analysis of the patients revealed a homogeneous group (n= 33) showing significantly higher expression levels of all four genes than the other patients. There was an about tenfold difference between the median values of this group of patients with mRNA high expression levels and the remainder for OPN (3.3 versus 0.4), TGF-β (2.0 versus 0.3), MMP2 (9.6 versus1.1), and Cox2 (20.8 versus 2.6) which was highly significant (p&amp;lt;0.001, respectively). However, there was no correlation between patients expressing high or low levels of these four genes and known parameters of clinical prognosis (UICC stages, mean survival time). In conclusion, tenfold increased expression levels of OPN, TGF-β, MMP2 and Cox2 in a subset of colorectal cancer patients did not predict for a clinical outcome that is different from that of the remaining patients. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1739.