Identification of Common Differentially Expressed Genes in Urinary Bladder Cancer

Apostolos Zaravinos,Demetrios A Spandidos,Ioannis Boulalas,Dimitris Delakas,George I Lambrou,Michael Polymenis

doi:10.1371/journal.pone.0018135

Abstract

BackgroundCurrent diagnosis and treatment of urinary bladder cancer (BC) has shown great progress with the utilization of microarrays.PurposeOur goal was to identify common differentially expressed (DE) genes among clinically relevant subclasses of BC using microarrays.Methodology/Principal FindingsBC samples and controls, both experimental and publicly available datasets, were analyzed by whole genome microarrays. We grouped the samples according to their histology and defined the DE genes in each sample individually, as well as in each tumor group. A dual analysis strategy was followed. First, experimental samples were analyzed and conclusions were formulated; and second, experimental sets were combined with publicly available microarray datasets and were further analyzed in search of common DE genes. The experimental dataset identified 831 genes that were DE in all tumor samples, simultaneously. Moreover, 33 genes were up-regulated and 85 genes were down-regulated in all 10 BC samples compared to the 5 normal tissues, simultaneously. Hierarchical clustering partitioned tumor groups in accordance to their histology. K-means clustering of all genes and all samples, as well as clustering of tumor groups, presented 49 clusters. K-means clustering of common DE genes in all samples revealed 24 clusters. Genes manifested various differential patterns of expression, based on PCA. YY1 and NFκB were among the most common transcription factors that regulated the expression of the identified DE genes. Chromosome 1 contained 32 DE genes, followed by chromosomes 2 and 11, which contained 25 and 23 DE genes, respectively. Chromosome 21 had the least number of DE genes. GO analysis revealed the prevalence of transport and binding genes in the common down-regulated DE genes; the prevalence of RNA metabolism and processing genes in the up-regulated DE genes; as well as the prevalence of genes responsible for cell communication and signal transduction in the DE genes that were down-regulated in T1-Grade III tumors and up-regulated in T2/T3-Grade III tumors. Combination of samples from all microarray platforms revealed 17 common DE genes, (BMP4, CRYGD, DBH, GJB1, KRT83, MPZ, NHLH1, TACR3, ACTC1, MFAP4, SPARCL1, TAGLN, TPM2, CDC20, LHCGR, TM9SF1 and HCCS) 4 of which participate in numerous pathways.Conclusions/SignificanceThe identification of the common DE genes among BC samples of different histology can provide further insight into the discovery of new putative markers.

Highlights

Cancer of the urinary bladder (BC) is the fifth most common cancer in men
TFBM Analysis In order to identify the transcription factors driving the observed changes in the gene expression, we investigated the Transcription Factor Binding Motifs (TFBMs) in the Transcription Element Listening System Database (TELiS) [33]
Our analysis showed that LHCGR was the most common differentially expressed (DE) gene found among the tumor samples

Summary

Introduction

Cancer of the urinary bladder (BC) is the fifth most common cancer in men. The peak prevalence of the disease is among patients 60–70 years of age. BC is curable if diagnosed during the early stages of the disease. 80% of BCs consist of superficial exophytic papillary lesions that originate from urothelial hyperplasia. These typically low-grade papillary tumors may recur, but rarely invade the bladder wall or metastasize. The remaining 15–20% of tumors represent high-grade solid nonpapillary BCs that arise from high-grade intraurothelial neoplasia. These tumors aggressively invade the bladder wall and have a high propensity for distant metastasis [1]. Purpose: Our goal was to identify common differentially expressed (DE) genes among clinically relevant subclasses of BC using microarrays

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Discussion

Conclusion