Comparative Network Analysis of Patients with Non-Small Cell Lung Cancer and Smokers for Representing Potential Therapeutic Targets

Abstract

Cigarette smoking is the leading cause of lung cancer worldwide. In this study, we evaluated the serum autoantibody (AAb) repertoires of non-small cell lung cancer (NSCLC) patients and smokers (SM), leading to the identification of overactivated pathways and hubs involved in the pathogenesis of NSCLC. Surface- and solution-phase biopanning were performed on immunoglobulin G purified from the sera of NSCLC and SM groups. In total, 20 NSCLC- and 12 SM-specific peptides were detected, which were used to generate NSCLC and SM protein datasets. NSCLC- and SM-related proteins were visualized using STRING and Gephi, and their modules were analyzed using Enrichr. By integrating the overrepresented pathways such as pathways in cancer, epithelial growth factor receptor, c-Met, interleukin-4 (IL-4) and IL-6 signaling pathways, along with a set of proteins (e.g. phospholipase D (PLD), IL-4 receptor, IL-17 receptor, laminins, collagens, and mucins) into the PLD pathway and inflammatory cytokines network as the most critical events in both groups, two super networks were made to elucidate new aspects of NSCLC pathogenesis and to determine the influence of cigarette smoking on tumour formation. Taken together, assessment of the AAb repertoires using a systems biology approach can delineate the hidden events involved in various disorders.

Cigarette smoke enhances oncogene addiction to c‐MET and desensitizes EGFR‐expressing non‐small cell lung cancer to EGFR TKIs

“…The receptor‐tyrosine kinase c‐MET is the receptor for hepatocyte growth factor (HGF) and activates a wide range of different cellular signaling pathways, including PI3K/Akt, MAPK, JNK, PKC and FAK, which contribute to proliferation, motility, migration and invasion (Organ and Tsao, ). In the network enrichment analysis, c‐MET has been identified as a hub which plays key roles in cancer initiation and progression of cigarette smoking‐associated NSCLC (Pazhouhandeh et al ., ). Activation of the HGF/c‐MET signaling pathway has also been found to be associated with a poor prognosis in various solid tumors including NSCLC (Guo et al ., ; Zhang et al ., ), indicating a predictive value for this disease.…”

Single cell and single nucleus RNA-Seq reveal cellular heterogeneity and homeostatic regulatory networks in adult mouse stria vascularis

“…Gene ontology analysis and gene enrichment analysis were performed using Enrichr (http://amp.pharm.mssm.edu/Enrichr/) as previously described (E. Y. Chen et al, 2013;Kuleshov et al, 2016;Pazhouhandeh et al, 2017). Enrichr is an integrated web-based application that includes updated gene-set libraries, alternative approaches to ranking enriched terms, and a variety of interactive visualization approaches to display the enrichment results.…”

A systems medicine approach reveals disordered immune system and lipid metabolism in multiple sclerosis patients

“…history of diseases in patients and their families) [20,21]. The blood level of C-reactive protein ( 6 mg/dl), erythrocyte sedimentation rate ( 32 mm/h), rheumatoid factor (negative RF), complete blood cell count and chest X-ray were examined in the patients.…”

“…The volunteers were interviewed to assess their demographic information and risk factors for autoimmune diseases and cancers (e.g. history of diseases in patients and their families) [20,21].…”

“…systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) [15][16][17][18][19]. Accordingly, we have evaluated the autoantibody repertories in patients with non-small-cell lung cancer [20], NHL [21], SLE, RA (in press) and MS to find common events and indeed common targets. With this background in mind, in the present study we employed a systems medicine approach to compare the autoantibody repertoires of newly diagnosed patients with RR-MS (NDP) and those receiving DMT (RP).…”