Integrative Analysis of microRNA, mRNA and DNA Copy Number Data Reveals Asbestos-Related Changes in Non-Small Cell Lung Cancer

ABSTRACT: Background: Lung cancer has the highest mortality rate of all the cancers in the world and asbestos-related lung cancer is one of the leading occupational cancers. The identification of the asbestos-related molecular changes has been a topic of major research interest over the years. The aim of the current study was to identify novel asbestos-related molecular correlates by integrating miRNA expression profiling with previously obtained microarray data (aCGH and mRNA expression) from the same patient material. Results: Twelve novel asbestos-related miRNAs (over-expressed: miR-148b, miR-374a, miR-24-1*, Let-7d, Let-7e, miR-199b-5p, miR-331-3p and under-expressed: miR-939, miR-671-5p, miR-605, miR-1224-5p, miR-202) which inversely correlated with target genes (e.g. GADD45A, LTBP1, FOSB, NCALD, CACNA2D2, MTSS1, EPB41L3) were identified. In addition, several known and new lung cancer-associated miRNAs were identified. DNA copy number alterations were also correlated with the deregulation of four miRNAs in lung cancer. The importance of integrated analysis was highlighted by the interesting finding of linking of the over-expression of well known squamous cell carcinoma-associated miR-205 with the down-regulation of the gene DOK4. Conclusions: Novel deregulated miRNAs and inversely correlating expression of target genes associated with lung cancer etiology and histology were identified. In addition, DNA copy number alterations correlated with the deregulation of some of the miRNAs. The results of the current study could have potential diagnostic implications, but require further investigation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE25508 | GEO | 2011/04/30

SECONDARY ACCESSION(S): PRJNA134653

REPOSITORIES: GEO