AUTHOR=Dimitrakopoulos Foteinos-Ioannis D. , Antonacopoulou Anna G. , Kottorou Anastasia E. , Kalofonou Melpomeni , Panagopoulos Nikolaos , Dougenis Dimitrios , Makatsoris Thomas , Tzelepi Vasiliki , Koutras Angelos , Kalofonos Haralabos P. 

TITLE=Genetic  Variations of CD40 and LTβR Genes Are Associated With Increased Susceptibility and Clinical Outcome of Non-Small-Cell Carcinoma Patients

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.721577

DOI=10.3389/fonc.2021.721577

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Immune system-related receptors CD40 (tumor necrosis factor receptor superfamily member 5), BAFFR (tumor necrosis factor receptor superfamily member 13C), and LTβR (tumor necrosis factor receptor superfamily member 3) play a pivotal role in non-small-cell lung cancer (NSCLC). To further evaluate their role in NSCLC, <italic>CD40</italic> rs1883832 (T&gt;C), <italic>BAFFR</italic> rs7290134 (A&gt;G), and <italic>LTβR</italic> rs10849448 (A&gt;G) single-nucleotide polymorphisms (SNPs) were investigated regarding their impact in risk and clinical outcome of NSCLC patients.</p></sec><sec><title>Methods</title><p>The three selected SNPs were evaluated in 229 NSCLC patients and 299 healthy controls, while CD40, BAFFR, and LTβR protein expression was assessed by immunohistochemistry in 96 tumor specimens from NSCLC patients.</p></sec><sec><title>Results</title><p>In total, <italic>CD40</italic> rs1883832 was associated with NSCLC risk, with the T allele, after adjusting for cofactors, being related to increased risk (p = 0.007; OR 1.701). Moreover, the CT genotype was associated with increased risk (p = 0.024; OR 1.606) and poorer 5-year overall survival (OS) after adjusting for cofactors (p = 0.001, HR 1.829), while CC was associated with higher CD40 expression in tumorous cells (p = 0.040) and in stromal cells (p = 0.036). In addition, AA homozygotes for the <italic>LTβR</italic> rs10849448 had increased risk for NSCLC in multivariate analysis (p = 0.008; OR, 2.106) and higher LTβR membranous expression (p = 0.035). Although <italic>BAFFR</italic> rs7290134 was associated with BAFFR membranous expression (p = 0.039), <italic>BAFFR</italic> rs7290134 was not associated with neither the disease risk nor the prognosis of NSCLC patients.</p></sec><sec><title>Conclusions</title><p>In conclusion, <italic>CD40</italic> rs1883832 and <italic>LTβR</italic> rs10849448 seem to be associated with increased risk for NSCLC, while <italic>CD40</italic> rs1883832 is also associated with OS of patients with NSCLC.</p></sec>