Spotlight on Differentially Expressed Genes in Urinary Bladder Cancer

Abstract

IntroductionWe previously identified common differentially expressed (DE) genes in bladder cancer (BC). In the present study we analyzed in depth, the expression of several groups of these DE genes.Materials and MethodsSamples from 30 human BCs and their adjacent normal tissues were analyzed by whole genome cDNA microarrays, qRT-PCR and Western blotting. Our attention was focused on cell-cycle control and DNA damage repair genes, genes related to apoptosis, signal transduction, angiogenesis, as well as cellular proliferation, invasion and metastasis. Four publicly available GEO Datasets were further analyzed, and the expression data of the genes of interest (GOIs) were compared to those of the present study. The relationship among the GOI was also investigated. GO and KEGG molecular pathway analysis was performed to identify possible enrichment of genes with specific biological themes.ResultsUnsupervised cluster analysis of DNA microarray data revealed a clear distinction in BC vs. control samples and low vs. high grade tumors. Genes with at least 2-fold differential expression in BC vs. controls, as well as in non-muscle invasive vs. muscle invasive tumors and in low vs. high grade tumors, were identified and ranked. Specific attention was paid to the changes in osteopontin (OPN, SPP1) expression, due to its multiple biological functions. Similarly, genes exhibiting equal or low expression in BC vs. the controls were scored. Significant pair-wise correlations in gene expression were scored. GO analysis revealed the multi-facet character of the GOIs, since they participate in a variety of mechanisms, including cell proliferation, cell death, metabolism, cell shape, and cytoskeletal re-organization. KEGG analysis revealed that the most significant pathway was that of Bladder Cancer (p = 1.5×10−31).ConclusionsThe present work adds to the current knowledge on molecular signature identification of BC. Such works should progress in order to gain more insight into disease molecular mechanisms.

Interleukin-20 Promotes Migration of Bladder Cancer Cells through Extracellular Signal-regulated Kinase (ERK)-mediated MMP-9 Protein Expression Leading to Nuclear Factor (NF-κB) Activation by Inducing the Up-regulation of p21WAF1 Protein Expression *

“…Many studies have demonstrated that the mutation of cell cycle inhibitory genes, such as p53, is associated with bladder cancer stage, progression, and prognosis (32,49). Recently, the importance of the expression of cyclin D1 and the shuttling of cyclin E during the development of bladder cancer has been demonstrated (50,51). Although previous reports have shown the role of the loss of p21 WAF1 expression in predicting poor outcomes in MIBC patients (31), these findings contradict others suggesting that p21 expression can provide a poor prognosis in patients with bladder cancer (52).…”

Gene expression is highly correlated on the chromosome level in urinary bladder cancer

“…Furthermore, in our pooled microarray analysis, a wide range of data from publicly available microarray data sets was included, increasing the total number to 129 bladder cancer and 17 control samples. Statistical analysis results were obtained from our previous works, 7,35 and the same collection of genes was used. All conclusions and further analyses were based on the differential gene expression reported.…”

“…In the first part, we performed microarray experimentation as previously described in detail 7,35 (Cohort A). The tumor samples were divided into three groups, as follows: T1-grade 2, T1-grade 3 and T2/T3-grade 3.…”

MicroRNA profiling in murine liver after partial hepatectomy

“…We clustered the miRNAs between the L0 and L12 murine livers, using hierarchical clustering (HCL) and k-means clustering, as previously reported (16,17).…”