MiRNA Profiling of Colorectal Carcinoma and Lymph Node Metastases
Stefan Costinean, Veronica Balatti, Paola Dama, Luciano Cascione, Jonathan Rock, Carlo M Croce, Wendy L Frankel. Ohio State University, Columbus, OH
Background: Colorectal cancer (CRC) is the third cause of death due to cancer in the US. Many of these deaths are due to the lack of early diagnosis and widespread metastases at the time of presentation. The molecular mechanisms of metastasis have been intensively studied in recent years. MiRNAs are involved in posttranscriptional regulation. Studies show that miRNAs are deregulated in cancer and could represent a genetic signature of normal and malignant tissues. Deregulation of specific miRNAs could be partially responsible for the metastatic potential of a tumor. Knowing the mechanism of metastasis has prognostic and therapeutic applicability. We compare miRNA profiles of microsatellite stable colorectal carcinomas (MSS-CRC) to corresponding lymph node (LN) metastases to assess differences.
Design: We selected 40 MSS-CRC and 42 corresponding LN metastases from the tissue archives. MSS-CRC were identified by previously documented intact mismatch repair proteins by immunohistochemistry. Representative areas of the tumors (primary and metastatic) were cored. RNA was analyzed using Nanostring.
Results: We identified 12 miRNAs deregulated in LN vs. the corresponding CRC. 6 miRNAs were upregulated in the LN compared to the CRC (miR150, miR142-3p, miR342-3p, miR195-5p, miR146-5p and miR4741) and 6 were downregulated (miR200a-3p, miR200b-3p, miR200c-3p, miR429 and miR196b-5p). Of these genes, mir150 seems to have the highest level of expression in the metastases compared to the primaries: 3.1 times more expressed in the LN compared to the CRC.
Conclusions: A limited number of miRNAs are markedly deregulated in the LN metastases compared with the CRC. MicroRNA miR150, a known repressor of the powerful p53 protein, was identified as being 3.1 times more expressed in the metastases compared to the primaries. In contrast, all 3 members of the miR200 family (a, b and c), targeting a large array of important transcription factors, were found downregulated in metastases compared to primaries. These miRNAs offer important insight into mechanisms possibly responsible for initiation of the metastatic process in CRC and might suggest novel molecular therapies.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 88, Wednesday Morning