Small RNA sequencing reveals metastasis-related microRNAs in lung adenocarcinoma
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Iben Daugaard1,2, Morten T. Venø2, Yan Yan2, Tina E. Kjeldsen1, Philippe Lamy4, Henrik Hager3,5, Jørgen Kjems2, Lise Lotte Hansen1
1Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark
2Department of Molecular Biology and Genetics, Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C, Denmark
3Department of Pathology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark
4Department of Molecular Medicine, Aarhus University Hospital, DK-8200 Aarhus N, Denmark
5Department of Clinical Pathology, Vejle Hospital, DK-7100 Vejle, Denmark
Iben Daugaard, email: firstname.lastname@example.org
Keywords: miRNA-seq, lung adenocarcinoma, metastasis, FFPE, microRNA
Received: August 08, 2016 Accepted: February 20, 2017 Published: March 07, 2017
The majority of lung cancer deaths are caused by metastatic disease. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression and miRNA dysregulation can contribute to metastatic progression. Here, small RNA sequencing was used to profile the miRNA and piwi-interacting RNA (piRNA) transcriptomes in relation to lung cancer metastasis. RNA-seq was performed using RNA extracted from formalin-fixed paraffin embedded (FFPE) lung adenocarcinomas (LAC) and brain metastases from 8 patients, and LACs from 8 patients without detectable metastatic disease. Impact on miRNA and piRNA transcriptomes was subtle with 9 miRNAs and 8 piRNAs demonstrating differential expression between metastasizing and non-metastasizing LACs. For piRNAs, decreased expression of piR-57125 was the most significantly associated with distant metastasis. Validation by RT-qPCR in a LAC cohort comprising 52 patients confirmed that decreased expression of miR-30a-3p and increased expression of miR-210-3p were significantly associated with the presence of distant metastases. miR-210-3p tumor cell specificity was evaluated by in situ hybridization and its biomarker potential was confirmed by ROC curve analysis (AUC = 0.839). Lastly, agreement between miRNA-seq and RT-qPCR for FFPE-derived RNA was evaluated and a high level of concordance was determined. In conclusion, this study has identified and validated metastasis-related miRNAs in LAC.
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