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. 2021 Sep 17:11:721577.
doi: 10.3389/fonc.2021.721577. eCollection 2021.

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

Foteinos-Ioannis D Dimitrakopoulos  1   2 , Anna G Antonacopoulou  2 , Anastasia E Kottorou  2 , Melpomeni Kalofonou  3 , Nikolaos Panagopoulos  4 , Dimitrios Dougenis  4 , Thomas Makatsoris  1 , Vasiliki Tzelepi  5 , Angelos Koutras  1 , Haralabos P Kalofonos  1
Affiliations

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

Foteinos-Ioannis D Dimitrakopoulos et al. Front Oncol. .

Abstract

Background: 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, CD40 rs1883832 (T>C), BAFFR rs7290134 (A>G), and LTβR rs10849448 (A>G) single-nucleotide polymorphisms (SNPs) were investigated regarding their impact in risk and clinical outcome of NSCLC patients.

Methods: 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.

Results: In total, CD40 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 LTβR rs10849448 had increased risk for NSCLC in multivariate analysis (p = 0.008; OR, 2.106) and higher LTβR membranous expression (p = 0.035). Although BAFFR rs7290134 was associated with BAFFR membranous expression (p = 0.039), BAFFR rs7290134 was not associated with neither the disease risk nor the prognosis of NSCLC patients.

Conclusions: In conclusion, CD40 rs1883832 and LTβR rs10849448 seem to be associated with increased risk for NSCLC, while CD40 rs1883832 is also associated with OS of patients with NSCLC.

Keywords: NSCLC; SNP; prognosis; risk; rs10849448; rs1883832; rs7290134.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier curves depicting overall survival (OS) of NSCLC patients in relation to (A) CD40 rs1883832 genotypes in the whole sub-cohort of NSCLC patients, (B) CD40 rs1883832 genotypes in SQ patients, (C) CD40 rs1883832 genotypes in ADC patients, (D) CD40 rs1883832 genotypes in stage I and II patients, (E) CD40 rs1883832 genotypes in NSCLC patients with N = 0, (F) CD40 rs1883832 genotypes in NSCLC patients with N = 1. SQ, squamous cell carcinoma; ADC, adenocarcinoma.
Figure 2
Figure 2
(A) Kaplan–Meier curves depicting 5-year OS of NSCLC patients in relation to CD40 mRNA levels as provided by KM plotter, (B) Kaplan–Meier curves depicting 5-year OS of NSCLC patients in relation to LTβR mRNA levels as provided by the KM plotter.
See this image and copyright information in PMC

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References

    1. Dimitrakopoulos FD, Kottorou AE, Kalofonou M, Kalofonos HP. The Fire Within: NF-KappaB Involvement in Non-Small Cell Lung Cancer. Cancer Res (2020) 80(19):4025–36. doi: 10.1158/0008-5472.CAN-19-3578 - DOI - PubMed
    1. Dimitrakopoulos FI, Antonacopoulou AG, Kottorou A, Vlotinou H, Panagopoulos ND, Dougenis D, et al. . NSCLC and the Alternative Pathway of NF-Kappab: Uncovering an Unknown Relation. Virchows Archiv: Int J Pathol (2012) 460(5):515–23. doi: 10.1007/s00428-012-1230-2 - DOI - PubMed
    1. Tang X, Liu D, Shishodia S, Ozburn N, Behrens C, Lee JJ, et al. . Nuclear Factor-KappaB (NF-Kappab) Is Frequently Expressed in Lung Cancer and Preneoplastic Lesions. Cancer (2006) 107(11):2637–46. doi: 10.1002/cncr.22315 - DOI - PubMed
    1. Zhang Z, Ma J, Li N, Sun N, Wang C. Expression of Nuclear factor-kappaB and Its Clinical Significance in Nonsmall-Cell Lung Cancer. Ann Thoracic Surg (2006) 82(1):243–8. doi: 10.1016/j.athoracsur.2006.01.049 - DOI - PubMed
    1. Dimitrakopoulos FD, Antonacopoulou AG, Kottorou AE, Panagopoulos N, Kalofonou F, Sampsonas F, et al. . Expression Of Intracellular Components of the NF-KappaB Alternative Pathway (NF-Kappab2, RelB, NIK and Bcl3) Is Associated With Clinical Outcome of NSCLC Patients. Sci Rep (2019) 9(1):14299. doi: 10.1038/s41598-019-50528-y - DOI - PMC - PubMed