Abstract
BackgroundMiRNA expression markers are well characterized in colorectal cancer (CRC), but less is known about miRNA expression profiles in colorectal adenomas. Genome-wide miRNA and mRNA expression analyses were conducted through the colorectal adenoma dysplasia sequence. Furthermore, analysis of the expression levels of miRNAs in matched plasma samples was performed, focusing on biomarker candidates; miRNA and mRNA expression analyses were performed on colorectal biopsies and plasma samples (20 normals; 11 tubular and 9 tubulovillous adenomas; 20 colorectal carcinomas) by miRNA 3.0 and Human Transcriptome Array (Affymetrix) and validated by RT-qPCR. Microarray data were analyzed using Expression Console and mRNA targets were predicted using miRWALK 2.0.ResultsBased on microarray analysis, 447 miRNAs were expressed in tissue and 320 in plasma. Twelve were upregulated (miR-31, 8-fold p < 0.001) and 11 were downregulated (miR-10b 3-fold p < 0.001) in neoplastic lesions compared to normal group. Eleven miRNAs showed altered expression between adenoma subtypes (miR-183 2.8-fold change, p < 0.007). Expression level of 24 miRNAs differed between adenoma and CRC groups (including miR-196a, 3.5-fold). Three miRNAs (miR-31, miR-4506, miR-452*) were differentially expressed in adenoma compared to normal both in tissue and plasma samples. miRNA expression data were confirmed by RT-PCR both in plasma and matched tissue samples.ConclusionsMiRNAs showed characteristic expression changes during CRC development in tissue. miRNAs were also presented in plasma and positively correlated with matched tissue expression levels. The identified miRNA expression changes could be verified RT-PCR methods facilitating routine application.
Highlights
MiRNA expression markers are well characterized in colorectal cancer (CRC), but less is known about miRNA expression profiles in colorectal adenomas
As Kinzler and Vogelstein described, tubular adenomas can transform into advanced adenomas with severe dysplasia and a high risk of malignant progression evolving to adenocarcinoma [5]
From the 1733 mature miRNA probe sets, 442 had positive values in normal tissue samples, 460 present values were detected in adenoma tissue samples, and 441 present values were detected in colorectal carcinoma tissue samples (Fig. 1)
Summary
MiRNA expression markers are well characterized in colorectal cancer (CRC), but less is known about miRNA expression profiles in colorectal adenomas. Genome-wide miRNA and mRNA expression analyses were conducted through the colorectal adenoma dysplasia sequence. Analysis of the expression levels of miRNAs in matched plasma samples was performed, focusing on biomarker candidates; miRNA and mRNA expression analyses were performed on colorectal biopsies and plasma samples (20 normals; 11 tubular and 9 tubulovillous adenomas; 20 colorectal carcinomas) by miRNA 3.0 and Human Transcriptome Array (Affymetrix) and validated by RTqPCR. In the classic model of tumorigenesis, CRC develops through polyps to cancer, starting with an early development to adenoma from an aberrant crypt foci followed by colorectal tumor progression. This multistep process is influenced by several. The adenoma-dysplasia-carcinoma sequence has been genetically well evaluated and explored by targeted and whole genome mutation analysis [6]
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