MicroRNA profile and KRAS status in metastatic colorectal cancer.
2011; Lippincott Williams & Wilkins; Volume: 29; Issue: 4_suppl Linguagem: Inglês
10.1200/jco.2011.29.4_suppl.453
ISSN1527-7755
AutoresManuel Valladares‐Ayerbes, M. Blanco, Margarita Reboredo, María José Lorenzo-Patiño, Francisco Arnal, M. Haz Conde, Vanessa Medina Villaamil, I. Santamarina Caínzos, Luis M. Antón Aparicio, Mar Martinez,
Tópico(s)Circular RNAs in diseases
Resumo453 Background: microRNAs (miRNAs) are small non-coding RNA with regulatory functions. miRNAs expression is deregulated in cancer. Our objective is to establish a miRNA expression profile as a prognostic and predictive signature in Colorectal Cancer (CRC). In this cohort, patients with metastatic (m) CRC have been included. The expression of miRNAs have been analyzed and correlated with clinical and pathologic parameters, including KRAS status, disease free survival (DFS), and overall survival (OS). Methods: Tissue samples of mCRC were obtained as formalin-fixed paraffin-embedded (FFPE) specimens from the archives of our institution, after obtaining informed consent of patients. Genomic DNA was extracted using Qiaamp DNA mini kit (Qiagen). For the mutational testing of KRAS gene, we use the TheraScreen KRAS PCR kit (Qiagen). miRNA-enriched RNA was extracted using High Pure miRNA Isolation Kit (Roche). miRNA expression was analyzed by quantitative reverse transcription PCR (RT-qPCR) using LNA technology (Exiqon) in a LightCycler 480 (Roche) device. REST2009 (Qiagen), SPSS 19 (IBM), and Prism (GraphPad) software was used to data analysis. Results: One-hundred and forty mCRC patients have been included. To date, we have extracted DNA and performed KRAS mutational testing for 127 FFPE specimens. From these, 72 (56.7%) were wt while the remaining 55 (43.3%) were mt. We have performed a miRNA expression studies in 28 tumors. miRNAs let-7a, miR-17, miR-21, and miR-200c were analyzed. 5S rRNA and U6 snRNA were amplified as reference genes. miR-21, miR-17, and let-7a were found upregulated (p<0.05) in mCRC samples versus healthy colon. However, for all 4 miRNAs analyzed, there were no significant differences of expression between wt and mt tumor samples for KRAS gene. Conclusions: The expression of 4 miRNAs analyzed is not correlated with mutations in KRAS gene. However, 3 of 4 miRNAs analyzed were found upregulated in tumors. The results for the association of the expression of miRNAs analyzed with the response to treatment and other clinical parameters will be presented during the symposium. Supported in part by SERGAS, Xunta de Galicia, Grant PS08/77. No significant financial relationships to disclose.
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