Abstract
Colorectal cancer (CRC) is one of the leading causes of death by cancer worldwide. Bowel cancer screening programs enable us to detect early lesions and improve the prognosis of patients with CRC. However, they also generate a significant number of problematic polyps, e.g., adenomas with epithelial misplacement (pseudoinvasion) which can mimic early adenocarcinoma. Therefore, biomarkers that would enable us to distinguish between adenoma with epithelial misplacement (pseudoinvasion) and adenoma with early adenocarcinomas (true invasion) are needed. We hypothesized that the former are genetically similar to adenoma and the latter to adenocarcinoma and we used bioinformatics approach to search for candidate genes that might be potentially used to distinguish between the two lesions. We used publicly available data from Gene Expression Omnibus database and we analyzed gene expression profiles of 252 samples of normal mucosa, colorectal adenoma, and carcinoma. In total, we analyzed 122 colorectal adenomas, 59 colorectal carcinomas, and 62 normal mucosa samples. We have identified 16 genes with differential expression in carcinoma compared to adenoma: COL12A1, COL1A2, COL3A1, DCN, PLAU, SPARC, SPON2, SPP1, SULF1, FADS1, G0S2, EPHA4, KIAA1324, L1TD1, PCKS1, and C11orf96. In conclusion, our in silico analysis revealed 16 candidate genes with different expression patterns in adenoma compared to carcinoma, which might be used to discriminate between these two lesions.
Highlights
Colorectal cancer (CRC) is developed by multistep process from normal epithelium to adenoma and adenocarcinoma, which can eventually metastasize to different organs [1]
We identified 172 genes overlapping in all projects for carcinoma compared to normal (568 in GSE10714, 845 in GSE37364, 1057 in GSE41657, and 806 in GSE50114 combind with GSE50115), 137 genes overlapping in all projects for adenoma compared to normal (530 in GSE10714, 412 in GSE37364, 927 in GSE41657, and 555 in GSE50114 combind with GSE50115), and 26 genes overlapping in all projects for carcinoma compared to adenoma (252 in GSE10714, 392 in GSE37364, 116 in GSE41657, and 348 in GSE50114 combind with GSE50115) (Figure 1)
We identified 16 gene expression patterns unique to carcinoma compared to adenoma, suggesting that these 16 genes have a role in promoting progression of adenoma to carcinoma
Summary
Colorectal cancer (CRC) is developed by multistep process from normal epithelium to adenoma and adenocarcinoma, which can eventually metastasize to different organs [1]. The model of development of CRC was introduced in 1990, where APC, KRAS, TP53, and DCC were proposed as genes promoting the progression of CRC [2]. Many studies have investigated underlying molecular mechanisms of CRC. It is accepted that CRC arises from accumulation of genetic and epigenetic events that alter signaling in pathways, such as Wnt, PIK3CA, and TGF-β. Three major accepted pathways in the pathogenesis of CRC are chromosome instability pathway, microsatellite instability pathway, and CpG island methylator phenotype. There are many CRCs that lack the changes described in above pathways, suggesting that other mechanisms are involved in the development of CRC [1]
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