title: Paired proteomics, transcriptomics and miRNomics in non-small cell lung cancers: known and novel signaling cascades.
abstract: High-throughput omics analyses are applied to elucidate molecular pathogenic mechanisms in cancer. Given restricted cohort sizes and contrasting large feature sets paired multi-omics analysis supports discovery of true positive deregulated signaling cascades. For lung cancer patients we measured from the same tissue biopsies proteomic- (6,183 proteins), transcriptomic- (34,687 genes) and miRNomic data (2,549 miRNAs). To minimize inter-individual variations case and control lung biopsies have been gathered from the same individuals.Considering single omics entities, 15 of 2,549 miRNAs (0.6%), 752 of 34,687 genes (2.2%) and 141 of 6,183 proteins (2.3%) were significantly deregulated. Multivariate analysis also revealed that effects in miRNA were smaller compared to genes and proteins indicating that expression changes of miRNAs might also have limited impact of pathogenicity. However, a new algorithm for modeling the complex mutual interactions of miRNAs and their target genes facilitated precise prediction of deregulation in cancer genes (92.3% accuracy, p=0.007). Lastly, deregulation of genes in cancer matched deregulation of proteins coded by the genes in 80% of cases.The resulting interaction network, which is based on quantitative analysis of the abundance of miRNAs, mRNAs and proteins each taken from the same lung cancer tissue and from the same autologous normal lung tissue confirms molecular pathological changes and further contributes to the discovery of altered signaling cascades in lung cancer.
authors: Chair for Clinical Bioinformatics, Saarland University, Germany.
authors: Christina
authors: C
authors: Backes
authors: Department of Human Genetics, Saarland University, Germany.
authors: Nicole
authors: N
authors: Ludwig
authors: Department of Human Genetics, Saarland University, Germany.
authors: Petra
authors: P
authors: Leidinger
authors: SHG Clinics, Völklingen, Germany.
authors: Hanno
authors: H
authors: Huwer
authors: Institute for Immunology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors: Stefan
authors: S
authors: Tenzer
authors: Chair for Clinical Bioinformatics, Saarland University, Germany.
authors: Tobias
authors: T
authors: Fehlmann
authors: IKMB, Kiel, Germany.
authors: Andre
authors: A
authors: Franke
authors: Department of Human Genetics, Saarland University, Germany.
authors: Eckart
authors: E
authors: Meese
authors: Chair for Bioinformatics, Saarland University, Germany.
authors: Hans-Peter
authors: HP
authors: Lenhof
authors: Chair for Clinical Bioinformatics, Saarland University, Germany.
authors: Andreas
authors: A
authors: Keller
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction / Q000502:physiology*; D059467:Transcriptome
chemical_list: D035683:MicroRNAs
keywords: lung cancer; miRNomics; proteomics; systems biology; transcriptomics