Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis

Abstract

Background Nasopharyngeal carcinoma (NPC) is a cancer of epithelial origin with a high incidence in certain populations. While NPC has a high remission rate with concomitant chemoradiation, recurrences are frequent, and the downstream morbidity of treatment is significant. Thus, it is imperative to find alternative therapies. Methods We employed a Search Tag Analyze Resource (STARGEO) platform to conduct a meta-analysis using the National Center for Biotechnology’s (NCBI) Gene Expression Omnibus (GEO) to define NPC pathogenesis. We identified 111 tumor samples and 43 healthy nasopharyngeal epithelium samples from NPC public patient data. We analyzed associated signatures in Ingenuity Pathway Analysis (IPA), restricting genes that showed statistical significance (p<0.05) and an absolute experimental log ratio greater than 0.15 between disease and control samples. Results Our meta-analysis identified activation of lipopolysaccharide (LPS)-induced tissue injury in NPC tissue. Additionally, interleukin-1 (IL-1) and SB203580 were the top upstream regulators. Tumorigenesis-related genes such as homeobox A10 (HOXA10) and prostaglandin-endoperoxide synthase 2 (PTGS2 or COX-2) as well as those associated with extracellular matrix degradation, such as matrix metalloproteinases 1 and 3 (MMP-1, MMP-3) were also upregulated. Decreased expression of genes that encode proteins associated with maintaining healthy nasal respiratory epithelium structural integrity, including sentan-cilia apical structure protein (SNTN) and lactotransferrin (LTF) was documented. Importantly, we found that etanercept inhibits targets upregulated in NPC and LPS induction, such as MMP-1, PTGS2, and possibly MMP-3. Conclusions Our analysis illustrates that nasal epithelial barrier dysregulation and maladaptive immune responses are key components of NPC pathogenesis along with LPS-induced tissue damage.

Effects of CIK Cell Therapy Combined with Camrelizumab on the Quality of Life in Patients with Nasopharyngeal Carcinoma and Analysis of Prognostic Factors

“…The tumor tissues release a large amount of immunosuppressive factors during growth to inhibit T lymphocytes from differentiating and being mature and to induce T cells from differentiating to suppressor T cells. As a result, the percentage of T cell subsets is decreased and specific cytotoxic T lymphocytes conducive to killing EB virus are absent, leading to the treatment failure finally [ 19 , 20 ]. Therefore, improving the patients' immune function is the emphasis of treating nasopharyngeal carcinoma in clinic.…”

Photodynamic Therapy Can Modulate the Nasopharyngeal Carcinoma Microenvironment Infected with the Epstein–Barr Virus: A Systematic Review and Meta-Analysis

“…IL-1 is a pro-inflammatory cytokine that participates in nasopharyngeal carcinoma development and is recognized as an oncogenic factor for this tumor. High IL-1 levels are normal in nasopharyngeal carcinoma and are stimulated by T cells infiltrated in the tumor and lipopolysaccharides (LPS) [39]. In this scenario, LPS-containing Gram-negative bacteria can stimulate resident macrophages via TLR4 for TNF and IL-1 secretion, inducing cell proliferation and tumorigenesis [40].…”

Screening Key Genes and Biological Pathways in Nasopharyngeal Carcinoma by Integrated Bioinformatics Analysis

“…The results of antibody staining showed that PTGS2 and MMP3 were strongly expressed in HSNC. A recent meta-analysis identified the upregulation of PTGS2, MMP1, and MMP3 in NPC tissues, shows that the maladjustment of nasal epithelial barrier and maladjusted immune response are the key components in the pathogenesis of NPC [ 22 ]. Another previous meta-analysis found that the overexpression of PTGS2 was significantly associated with a low survival rate in patients with NPC [ 23 ].…”