Identification of key genes for carcinogenic pathways associated with colorectal adenoma-to-carcinoma progression - PubMed (original) (raw)

Identification of key genes for carcinogenic pathways associated with colorectal adenoma-to-carcinoma progression

Anke H Sillars-Hardebol et al. Tumour Biol. 2010 Apr.

Abstract

Colorectal adenomas form a biologically and clinically distinct intermediate stage in development of colorectal cancer (CRC) from normal colon epithelium. Only 5% of adenomas progress into adenocarcinomas, indicating that malignant transformation requires other biological alterations than those involved in adenoma formation. The present study aimed to explore which cancer-related biological processes are affected during colorectal adenoma-to-carcinoma progression and to identify key genes within these pathways that can serve as tumor markers for malignant transformation. The activity of 12 cancer-related biological processes was compared between 37 colorectal adenomas and 31 adenocarcinomas, using the pathway analysis tool Gene Set Enrichment Analysis. Expression of six gene sets was significantly increased in CRCs compared to adenomas, representing chromosomal instability, proliferation, differentiation, invasion, stroma activation, and angiogenesis. In addition, 18 key genes were identified for these processes based on their significantly increased expression levels. For AURKA and PDGFRB, increased mRNA expression levels were verified at the protein level by immunohistochemical analysis of a series of adenomas and CRCs. This study revealed cancer-related biological processes whose activities are increased during malignant transformation and identified key genes which may be used as tumor markers to improve molecular characterization of colorectal tumors.

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Figures

Fig. 1

Fig. 1

Comparison of mRNA expression levels for key genes of pathway activity in colorectal adenomas and CRCs. Boxplots showing mRNA expression levels of 37 colorectal adenomas and 31 colorectal adenocarcinomas, based on oligonucleotide microarray expression data. Expression of key genes was significantly higher in CRC compared to adenomas (p values < 1e-5). a AURKA; b PLK1; c ADRM1; d SSSCA1; e SPARC; and f PDGFRB

Fig. 2

Fig. 2

Comparison of protein expression levels for AURKA and PDGFRB in colorectal adenomas and CRCs. Immunohistochemical stainings for AURKA and PDGFRB confirmed overexpression of both proteins in CRCs compared to colorectal adenomas. AURKA staining can be found in the epithelial cells, while PDGFRB expression is observed in tumor stroma. Representative examples of AURKA and PDGFRB staining are shown for colorectal adenoma and carcinoma tissue. Digital images were obtained with a 20× objective (AURKA) and a 10× objective (PDGFRB)

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