Identification and Validation of Commonly Overexpressed Genes in Solid Tumors by Comparison of Microarray Data

Abstract

Cancers originating from epithelial cells are the most common malignancies. No common expression profile of solid tumors compared to normal tissues has been described so far. Therefore we were interested if genes differentially expressed in the majority of carcinomas could be identified using bioinformatic methods. Complete data sets were downloaded for carcinomas of the prostate, breast, lung, ovary, colon, pancreas, stomach, bladder, liver, and kidney, and were subjected to an expression analysis using SAM. In each experiment, a gene was scored as differentially expressed if the q value was below 25%. Probe identifiers were unified by comparing the respective probe sequences to the Unigene build 155 using BlastN. To obtain differentially expressed genes within the set of analyzed carcinomas, the number of experiments in which differential expression was observed was counted. Differential expression was assigned to genes if they were differentially expressed in at least eight experiments of tumors from different origin. The identified candidate genes ADRM1, EBNA1BP2, FDPS, FOXM1, H2AFX, HDAC3, IRAK1, and YY1 were subjected to further validation. Using this comparative approach, 100 genes were identified as upregulated and 21 genes as downregulated in the carcinomas.

Phenotype-assisted transcriptome analysis identifies FOXM1 downstream from Ras–MKK3–p38 to regulate in vitro cellular invasion

“…Our results provide novel and compelling evidence that FOXM1, a forkhead/winged-helix transcription factor that is specifically upregulated in a broad variety of cancers, that is, colon, prostate, pancreas and lung cancers (Pilarsky et al, 2004;Kalin et al, 2006;Yoshida et al, 2007), functions downstream of this cascade and is required for regulation of invasion and anchorage-independent growth. It is tempting to speculate that FOXM1 serves as one of the major relay stations for the induction of invasion by signals through the Ras-p38 pathway and that cellular phenotype decisions may in part depend on FOXM1.…”

“…FOXM1 is a forkhead/winged-helix transcription factor that is specifically upregulated in a broad variety of cancers, that is, colon, prostate, pancreas and lung cancers (Pilarsky et al, 2004;Kalin et al, 2006;Yoshida et al, 2007). Moreover, this transcription factor appears to play a major role in early tumorigenesis of head and neck squamous cell cancers (Gemenetzidis et al, 2009) and seems not to induce apoptosis (Kalinina et al, 2003;Gusarova et al, 2007;Park et al, 2009).…”

Transgenic expression of the forkhead box M1 transcription factor induces formation of lung tumors

“…Consistent with an important role of Foxm1 in cell cycle progression, increased expression of Foxm1 was found in human lung adenocarcinomas and squamous cell carcinomas (Kim et al, 2006), prostate adenocarcinomas , basal cell carcinomas (Teh et al, 2002), intrahepatic cholangiocarcinomas (Obama et al, 2005), anaplastic astrocytomas and glioblastomas (van den Boom et al, 2003), infiltrating ductal breast carcinomas (Wonsey and Follettie, 2005), as well as in many other solid tumors (Pilarsky et al, 2004). Foxm1 is also overexpressed in hepatocellular carcinomas from patients who respond poorly to treatment (Lee et al, 2004).…”

Runx2 Protein Represses Axin2 Expression in Osteoblasts and Is Required for Craniosynostosis in Axin2-deficient Mice*

“…Biological interaction between Axin2, Runx2, and Hdac3 may also factor into disease mechanisms in cancer. Inactivating mutations in AXIN2 are associated with an increased incidence of several types of cancer because of unchecked Wnt signaling (51-54), whereas RUNX2 is highly expressed in breast and prostate cancers predisposed to skeletal metastasis (55,56), and HDAC3 is one of the most commonly up-regulated genes in human solid tumors (57). These observations are consistent with our data showing that Runx2 represses Axin2 in an Hdac3-dependent manner in vivo and suggest that this interaction may have biological relevance with respect to modulating Wnt/␤-catenin signaling in both skeletal development and cancer.…”