Gene expression profiling of esophageal cancer: Comparative analysis of Barrett's esophagus, adenocarcinoma, and squamous cell carcinoma

Abstract

Esophageal cancer is a particularly aggressive tumor with poor prognosis, however, our current knowledge of the genes and pathways involved in tumorigenesis of the esophagus are limited. To obtain insight into the molecular processes underlying tumorigenesis of the esophagus, we have used cDNA microarrays to compare the gene expression profiles of 128 tissue samples representing the major histological subtypes of esophageal cancer (squamous cell carcinoma and adenocarcinoma (ADC)) as well as Barrett's esophagus (BE), the precursor lesion to ADC, and normal esophageal epithelium. Linear discriminant analysis and unsupervised hierarchical clustering show the separation of samples into 4 distinct groups consistent with their histological subtype. Differentially expressed genes were identified between each of the tissue types. Comparison of gene ontologies and gene expression profiles identified gene profiles specific to esophageal cancer, as well as BE. “Esophageal cancer clusters,” representing proliferation, immune response, and extracellular matrix genes were identified, as well as digestion, hydrolase, and transcription factor clusters specific to the columnar phenotype observed during BE and esophageal ADC. These clusters provide valuable insight into the molecular and functional differences between normal esophageal epithelium, BE, and the 2 histologically distinct forms of esophageal cancers. Our thorough, unbiased analysis provides a rich source of data for further studies into the molecular basis of tumorigenesis of the esophagus, as well as identification of potential biomarkers for early detection of progression. © 2007 Wiley‐Liss, Inc.

Screening of microsatellite markers in penile cancer reveals differences between metastatic and nonmetastatic carcinomas

“…Interestingly, none of the examined carcinomas showed a combination of LOH in D17S786 and D12S101 (p53 and mdm2 region, both part of the p14 ARF /MDM2/p53 pathway). [42][43][44] In addition, we were able to show a significant association between high frequency of LOH and metastasis for penile carcinomas. Carcinomas with 10 and more affected markers showed a significant higher risk for metastasis (P ¼ 0.004).…”

“…A possible explanation for this result could be that sarcomatoid carcinomas resemble the more aggressive sarcomas, whereas basaloid variants still show the more structured histology of squamous carcinomas. As some authors speculate about a molecular genetic background for the differences between subtypes of squamous cell carcinomas and some molecular genetic differences have already been demonstrated, [41][42][43][44] further analysis of additional markers and chromosomal regions should be carried out to detect DNA aberrations that characterize aggressive variants.…”

Influence of genetics on tumoral pathologies: The example of the adenocarcinoma arising in Barrett's esophagus

“…For this reason understanding the steps leading to cancer and studying prognostic and diagnostic markers for tumor progression provide novel target for gene therapy. Nowadays a lot of techniques help us in studying the cancer development such as comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), immunohistochemistry (IHC); but some of the last methodologies (gene microarrays, gene expression profiling) allowed us to identify more genes specifically involved in this process (7). The cause of metaplasia is presumably a chance in expression of genes whose normal function is to distinguish the two tissue types in normal development (6).…”

Proteomic Study of Esophageal Squamous Cell Carcinoma

“…Extensive molecular biology studies of ESCC have identified a wealth of dysregulated molecular events involved in esophageal carcinogenesis, which cover a broad range of genes www.intechopen.com with diverse functions, such as vulnerable genes to chemicals, tumor-related genes, tumor suppressor genes, metastasis genes, apoptosis gene, proliferation genes, etc [Enzinger & Mayer, 2003;Greenawalt et al, 2007;Kwong, 2005;Lin et al, 2009]. Moreover, epigenetic alterations, chromosomal changes and transcriptional changes have also been found to play crucial roles in the pathogenesis of ESCC [Abnet et al, 2010;Greenawalt et al, 2007;.…”

“…Moreover, epigenetic alterations, chromosomal changes and transcriptional changes have also been found to play crucial roles in the pathogenesis of ESCC [Abnet et al, 2010;Greenawalt et al, 2007;. Although these findings improve our general understanding about the molecular biology of ESCC, the appropriate biomarkers for high-risk population screening, for clinical diagnosis and prognosis, for evaluation of treatment efficiency have not been identified yet.…”