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.
Highlights
Non-Hodgkin lymphoma (NHL) constitutes a highly heterogeneous group of lymphoproliferative malignancies, arising from both B and T lymphocytes, as well as natural killer cells [1, 2]
To determine immunoglobulins G (IgG) antibodies, which are only present in the sera of NHL patients, we enrolled a large healthy population to remove AAbs which may be found in the serum of healthy subjects and affect the results
The greatest signals were observed in the phages of the third round of panning on the purified IgG of NHL patients
Summary
Non-Hodgkin lymphoma (NHL) constitutes a highly heterogeneous group of lymphoproliferative malignancies, arising from both B and T lymphocytes, as well as natural killer cells [1, 2]. 70 800 new cases of NHL were identified in the USA in 2014, 96 788 new cases were diagnosed in Europe in 2015, and different occurrences have been reported in various countries. NHL remains among the top 10 most frequent cancers in the world [3]. In many NHL subtypes, timely diagnosis can result in effective and often curative treatment [4]. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) are the treatment of choice for different subtypes of NHL. Many patients with relapsed or primary refractory NHL cannot be treated by standard therapy, and generally show poor prognosis [3, 5]
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