Comparison of Circulating miRNAs Expression Alterations in Matched Tissue and Plasma Samples During Colorectal Cancer Progression
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MicroRNAs (miRNAs) have been found to play a critical role in colorectal adenoma-carcinoma sequence. MiRNA-specific high-throughput arrays became available to detect promising miRNA expression alterations even in biological fluids, such as plasma samples, where miRNAs are stable. The purpose of this study was to identify circulating miRNAs showing altered expression between normal colonic (N), tubular adenoma (ADT), tubulovillous adenoma (ADTV) and colorectal cancer (CRC) matched plasma and tissue samples. Sixteen peripheral plasma and matched tissue biopsy samples (N n = 4; ADT n = 4; ADTV n = 4; CRC n = 4) were selected, and total RNA including miRNA fraction was isolated. MiRNAs from plasma samples were extracted using QIAamp Circulating Nucleic Acid Kit (Qiagen). Matched tissue-plasma miRNA microarray experiments were conducted by GeneChip® miRNA 3.0 Array (Affymetrix). RT-qPCR (microRNA Ready-to-use PCR Human Panel I + II; Exiqon) was used for validation. Characteristic miRNA expression alterations were observed in comparison of AD and CRC groups (miR-149*, miR-3196, miR-4687) in plasma samples. In the N vs. CRC comparison, significant overexpression of miR-612, miR-1296, miR-933, miR-937 and miR-1207 was detected by RT-PCR (p < 0.05). Similar expression pattern of these miRNAs were observed using microarray in tissue pairs, as well. Although miRNAs were also found in circulatory system in a lower concentration compared to tissues, expression patterns slightly overlapped between tissue and plasma samples. Detected circulating miRNA alterations may originate not only from the primer tumor but from other cell types including immune cells.
KeywordsmicroRNA Plasma Circulating microRNA Colorectal cancer Colorectal adenoma Microarray Real-time PCR Tissue
This study was supported by the National Research, Development and Innovation Office (KMR-12-1-2012-0216 grant) and Hungarian Scientific Research Fund (OTKA-K111743) grant.
Compliance with Ethical Standards
All authors read and approved the final manuscript.
Conflict of Interest
The Authors declare that there is no conflict of interest.
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