A Systems Medicine Approach for Finding Target Proteins Affecting Treatment Outcomes in Patients With Non-Hodgkin Lymphoma Publisher Pubmed



Ajorloo F^{1, 2} ; Vaezi M³ ; Saadat A⁴ ; Safaee SR⁵ ; Gharib B⁶ ; Ghanei M^{2, 7} ; Siadat SD^{2, 8} ; Vaziri F^{2, 8} ; Fateh A^{2, 8} ; Pazhouhandeh M² ; Vaziri B⁹ ; Moazemi R⁹ ; Mahboudi F⁹ ; Jamnani FR^{2, 8} Show Affiliations
Source: PLoS ONE Published:2017

Abstract

Autoantibody profiling with a systems medicine approach can help identify critical dysregulated signaling pathways (SPs) in cancers. In this way, immunoglobulins G (IgG) purified from the serum samples of 92 healthy controls, 10 pre-treated (PR) non-Hodgkin lymphoma (NHL) patients, and 20 NHL patients who underwent chemotherapy (PS) were screened with a phage-displayed random peptide library. Protein-protein interaction networks of the PR and PS groups were analyzed and visualized by Gephi. The results indicated AXIN2, SENP2, TOP2A, FZD6, NLK, HDAC2, HDAC1, and EHMT2, in addition to CAMK2A, PLCG1, PLCG2, GRM5, GRIN2B, GRIN2D, CACNA2D3, and SPTAN1 as hubs in 11 and 7 modules of PR and PS networks, respectively. PR- and PS-specific hubs were evaluated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. The PR-specific hubs were involved in Wnt SP, signaling by Notch1 in cancer, telomere maintenance, and transcriptional misregulation. In contrast, glutamate receptor SP, Fc receptor-related pathways, growth factors-related SPs, and Wnt SP were statistically significant enriched pathways, based on the pathway analysis of PS hubs. The results revealed that the most PR-specific proteins were associated with events involved in tumor development, while chemotherapy in the PS group was associated with side effects of drugs and/or cancer recurrence. As the findings demonstrated, PR- and PS-specific proteins in this study can be promising therapeutic targets in future studies. © 2017 Ajorloo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.