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.

Figure 1

(A) Histogram of the number of genes analyzed by the different experiments. (B and C) Histogram of the number of genes found to be differentially expressed in the different experiments: (B) overexpressed; (C) underexpressed. Interestingly, we did not find a gene that is underexpressed in more than nine experiments, indicating a more heterogeneous gene expression in normal tissues of different origins. X-axis: number of experiments; Y-axis: number of genes.

Figure 2

(A) A total of 121 common differentially expressed genes. Red: Overexpressed in tumors; green: underexpressed in tumors; black: not differentially expressed; grey: not investigated in the original study. Within our comparison, values of +1 for overexpression and -1 for underexpression are assigned. Therefore, no graduations of differential expression are shown. (B) Heatmap of expression of the selected genes on the CPA II. Intensity values for the gene of interest were normalized by the value of β-actin of the respective probe and then divided by the normalized value of the corresponding normal tissue.

Figure 3

Grouping of identified genes into the molecular function categories of gene ontology using Fatigo (http://fatigo.bioinfo.cnio.es/). Red: Genes overexpressed in tumors; green genes underexpressed in tumors.