Integrative analysis of microRNA, mRNA and aCGH data reveals asbestos‐ and histology‐related changes in lung cancer

• DOI: 10.1002/gcc.20880
• Publication Date: 2011-05-11T17:30:48Z
• Authors: Penny Nymark; Mohamed Guled; Ioana Borze; Ali Faisal; Leo Lahti; Kaisa Salmenkivi; Eeva Kettunen; Sisko Anttila; Sakari Knuutila
• Keywords: Adult; Male; 0301 basic medicine; Comparative Genomic Hybridization; Lung Neoplasms; Gene Expression Profiling; Asbestos; Middle Aged; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Humans; RNA, Messenger; Aged

Lung cancer has the highest mortality rate of all cancers in world and asbestos-related lung is one leading occupational cancers. The identification molecular changes long been a topic increasing research interest. aim this study was to identify novel correlates by integrating miRNA expression profiling with previously obtained data (aCGH mRNA expression) from same patient material. performed on 26 tumor corresponding normal tissue samples highly asbestos-exposed non-exposed patients, eight control samples. Data analyses expression, integration were using Chipster. A separate analysis used integrate aCGH data. Both known new cancer-associated miRNAs target genes inverse correlation discovered. Furthermore, DNA copy number alterations (e.g., gain at 12p13.31) correlated deregulated miRNAs. Specifically, thirteen (over-expressed: miR-148b, miR-374a, miR-24-1*, Let-7d, Let-7e, miR-199b-5p, miR-331-3p, miR-96 under-expressed: miR-939, miR-671-5p, miR-605, miR-1224-5p miR-202) inversely GADD45A, LTBP1, FOSB, NCALD, CACNA2D2, MTSS1, EPB41L3) identified. In addition, over-expression well squamous cell carcinoma-associated miR-205 linked down-regulation DOK4 gene. miRNAs/genes presented here may represent interesting targets for further investigation could eventually have potential diagnostic implications.