Background: Psoriasis is complex inflammatory skin pathology of autoimmune origin. Several cell types are perturbed in this pathology, and underlying signaling events are complex and still poorly understood.Results: In order to gain insight into molecular machinery underlying the disease, we conducted a comprehensive meta-analysis of proteomics and transcriptomics of psoriatic lesions from independent studies. Network-based analysis revealed similarities in regulation at both proteomics and transcriptomics level. We identified a group of transcription factors responsible for overexpression of psoriasis genes and a number of previously unknown signaling pathways that may play a role in this process. We also evaluated functional synergy between transcriptomics and proteomics results.Conclusions: We developed network-based methodology for integrative analysis of high throughput data sets of different types. Investigation of proteomics and transcriptomics data sets on psoriasis revealed versatility in regulatory machinery underlying pathology and showed complementarities between two levels of cellular organization.

The level of acute-phase serum amyloid A (SAA) protein in human blood dramatically grows in cancer, often at its early stage, when acute inflammatory signs are not observed. This fact was registered both by immunochemistry and by proteomics methods in different common cancers, such as lung, ovarian, renal, uterine, and nasopharyngeal cancer and in melanoma. It was proposed that SAA is produced by liver in such cases, as in inflammation, high levels of SAA being a part of nonspecific response to tumor. However, that was not always true, because, in many cancers, the protein of interest is produced directly by cancer cells. What is the biological significance of this observation? What preferences do cancer cells obtain due to SAA overexpression? Recent data on melanoma patients have shown that serum amyloid A is able to stimulate immunosuppressive neutrophils to produce interleukin-10 cytokine that suppressed cell immunity. The ability of cancer cells to produce SAA that is acquired during cancer mutagenesis is likely to enhance their resistance to T-cell immunity due to activation of immunosuppressive granulocytes.

Oncolytic viruses have gained momentum in the last decades as a promising tool for cancer treatment. Despite the progress, only a fraction of patients show a positive response to viral therapy. One of the key variable factors contributing to therapy outcomes is interferon-dependent antiviral mechanisms in tumor cells. Here, we evaluated this factor using patient-derived glioblastoma multiforme (GBM) cultures. Cell response to the type I interferons’ (IFNs) stimulation was characterized at mRNA and protein levels. Omics analysis revealed that GBM cells overexpress interferon-stimulated genes (ISGs) and upregulate their proteins, similar to the normal cells. A conserved molecular pattern unambiguously differentiates between the preserved and defective responses. Comparing ISGs’ portraits with titration-based measurements of cell sensitivity to a panel of viruses, the “strength” of IFN-induced resistance acquired by GBM cells was ranked. The study demonstrates that suppressing a single ISG and encoding an essential antiviral protein, does not necessarily increase sensitivity to viruses. Conversely, silencing IFIT3 and PLSCR1 genes in tumor cells can negatively affect the internalization of vesicular stomatitis and Newcastle disease viruses. We present evidence of a complex relationship between the interferon response genes and other factors affecting the sensitivity of tumor cells to viruses.