Expression Of Intracellular Components of the NF-κB Alternative Pathway (NF-κB2, RelB, NIK and Bcl3) is Associated With Clinical Outcome of NSCLC Patients

Abstract A growing number of studies has shed light on the role of the NF-κΒ in non-small-cell lung cancer (NSCLC). To address the significance of major effectors of the NF-κΒ alternative pathway, we investigated the relationship between NF-κΒ2, RelB, NIK and Bcl3 expression (mRNA and protein) and t...

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Autores principales: Foteinos-Ioannis D. Dimitrakopoulos, Anna G. Antonacopoulou, Anastasia E. Kottorou, Nikolaos Panagopoulos, Fotini Kalofonou, Fotios Sampsonas, Chrisoula Scopa, Melpomeni Kalofonou, Angelos Koutras, Thomas Makatsoris, Dimitrios Dougenis, Helen Papadaki, Malcolm Brock, Haralabos P. Kalofonos
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spelling oai:doaj.org-article:90d7b523d73d42dd8591096c779df15c2021-12-02T15:09:53ZExpression Of Intracellular Components of the NF-κB Alternative Pathway (NF-κB2, RelB, NIK and Bcl3) is Associated With Clinical Outcome of NSCLC Patients10.1038/s41598-019-50528-y2045-2322https://doaj.org/article/90d7b523d73d42dd8591096c779df15c2019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50528-yhttps://doaj.org/toc/2045-2322Abstract A growing number of studies has shed light on the role of the NF-κΒ in non-small-cell lung cancer (NSCLC). To address the significance of major effectors of the NF-κΒ alternative pathway, we investigated the relationship between NF-κΒ2, RelB, NIK and Bcl3 expression (mRNA and protein) and the clinical outcome of NSCLC patients. NF-κΒ2, RelB, NIK and Bcl3 protein expression levels were assessed by immunohistochemistry in tissue samples from 151 NSCLC patients who had curative resection. mRNA levels were also evaluated in 69 patients using quantitative real-time PCR. Although all studied proteins were overexpressed in NSCLC (P < 0.001 for all), only RelB mRNA levels were strongly increased in cancerous specimens compared to tumor-adjacent non-neoplastic tissues (P = 0.009). Moreover, NF-κB2, RelB and Bcl3 expression was associated with overall survival (OS). In particular, cytoplasmic and mRNA expression of RelB was related to 5-year OS (P = 0.014 and P = 0.006, respectively). Multivariate analysis also showed that Bcl3 expression (nuclear and cytoplasmic) was associated with increased 5-year OS (P = 0.002 and P = 0.036, respectively). In addition, higher Bcl3 mRNA levels were associated with inferior OS in stages I & II and improved OS in stages III and IV after 5-year follow-up (P = 0.004 and P = 0.001, respectively). Furthermore, stage I patients with lower NF-κB2 mRNA levels had better 5-year survival in univariate and multivariate analysis (P = 0.031 and P = 0.028, respectively). Interestingly, RelB expression (cytoplasmic and mRNA) was inversely associated with relapse rates (P = 0.027 and P = 0.015, respectively), while low NIK cytoplasmic expression was associated with lower relapse rates (P = 0.019). Cytoplasmic NIK expression as well as NF-κB2/ Bcl3 detection was associated with lymph node infiltration (P = 0.039 and P = 0.014, respectively). The present study confirms the deregulation of the NF-κB alternative pathway in NSCLC and also demonstrates the importance of this pathway in prognosis, recurrence and infiltration of regional lymph nodes.Foteinos-Ioannis D. DimitrakopoulosAnna G. AntonacopoulouAnastasia E. KottorouNikolaos PanagopoulosFotini KalofonouFotios SampsonasChrisoula ScopaMelpomeni KalofonouAngelos KoutrasThomas MakatsorisDimitrios DougenisHelen PapadakiMalcolm BrockHaralabos P. KalofonosNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Foteinos-Ioannis D. Dimitrakopoulos
Anna G. Antonacopoulou
Anastasia E. Kottorou
Nikolaos Panagopoulos
Fotini Kalofonou
Fotios Sampsonas
Chrisoula Scopa
Melpomeni Kalofonou
Angelos Koutras
Thomas Makatsoris
Dimitrios Dougenis
Helen Papadaki
Malcolm Brock
Haralabos P. Kalofonos
Expression Of Intracellular Components of the NF-κB Alternative Pathway (NF-κB2, RelB, NIK and Bcl3) is Associated With Clinical Outcome of NSCLC Patients
description Abstract A growing number of studies has shed light on the role of the NF-κΒ in non-small-cell lung cancer (NSCLC). To address the significance of major effectors of the NF-κΒ alternative pathway, we investigated the relationship between NF-κΒ2, RelB, NIK and Bcl3 expression (mRNA and protein) and the clinical outcome of NSCLC patients. NF-κΒ2, RelB, NIK and Bcl3 protein expression levels were assessed by immunohistochemistry in tissue samples from 151 NSCLC patients who had curative resection. mRNA levels were also evaluated in 69 patients using quantitative real-time PCR. Although all studied proteins were overexpressed in NSCLC (P < 0.001 for all), only RelB mRNA levels were strongly increased in cancerous specimens compared to tumor-adjacent non-neoplastic tissues (P = 0.009). Moreover, NF-κB2, RelB and Bcl3 expression was associated with overall survival (OS). In particular, cytoplasmic and mRNA expression of RelB was related to 5-year OS (P = 0.014 and P = 0.006, respectively). Multivariate analysis also showed that Bcl3 expression (nuclear and cytoplasmic) was associated with increased 5-year OS (P = 0.002 and P = 0.036, respectively). In addition, higher Bcl3 mRNA levels were associated with inferior OS in stages I & II and improved OS in stages III and IV after 5-year follow-up (P = 0.004 and P = 0.001, respectively). Furthermore, stage I patients with lower NF-κB2 mRNA levels had better 5-year survival in univariate and multivariate analysis (P = 0.031 and P = 0.028, respectively). Interestingly, RelB expression (cytoplasmic and mRNA) was inversely associated with relapse rates (P = 0.027 and P = 0.015, respectively), while low NIK cytoplasmic expression was associated with lower relapse rates (P = 0.019). Cytoplasmic NIK expression as well as NF-κB2/ Bcl3 detection was associated with lymph node infiltration (P = 0.039 and P = 0.014, respectively). The present study confirms the deregulation of the NF-κB alternative pathway in NSCLC and also demonstrates the importance of this pathway in prognosis, recurrence and infiltration of regional lymph nodes.
format article
author Foteinos-Ioannis D. Dimitrakopoulos
Anna G. Antonacopoulou
Anastasia E. Kottorou
Nikolaos Panagopoulos
Fotini Kalofonou
Fotios Sampsonas
Chrisoula Scopa
Melpomeni Kalofonou
Angelos Koutras
Thomas Makatsoris
Dimitrios Dougenis
Helen Papadaki
Malcolm Brock
Haralabos P. Kalofonos
author_facet Foteinos-Ioannis D. Dimitrakopoulos
Anna G. Antonacopoulou
Anastasia E. Kottorou
Nikolaos Panagopoulos
Fotini Kalofonou
Fotios Sampsonas
Chrisoula Scopa
Melpomeni Kalofonou
Angelos Koutras
Thomas Makatsoris
Dimitrios Dougenis
Helen Papadaki
Malcolm Brock
Haralabos P. Kalofonos
author_sort Foteinos-Ioannis D. Dimitrakopoulos
title Expression Of Intracellular Components of the NF-κB Alternative Pathway (NF-κB2, RelB, NIK and Bcl3) is Associated With Clinical Outcome of NSCLC Patients
title_short Expression Of Intracellular Components of the NF-κB Alternative Pathway (NF-κB2, RelB, NIK and Bcl3) is Associated With Clinical Outcome of NSCLC Patients
title_full Expression Of Intracellular Components of the NF-κB Alternative Pathway (NF-κB2, RelB, NIK and Bcl3) is Associated With Clinical Outcome of NSCLC Patients
title_fullStr Expression Of Intracellular Components of the NF-κB Alternative Pathway (NF-κB2, RelB, NIK and Bcl3) is Associated With Clinical Outcome of NSCLC Patients
title_full_unstemmed Expression Of Intracellular Components of the NF-κB Alternative Pathway (NF-κB2, RelB, NIK and Bcl3) is Associated With Clinical Outcome of NSCLC Patients
title_sort expression of intracellular components of the nf-κb alternative pathway (nf-κb2, relb, nik and bcl3) is associated with clinical outcome of nsclc patients
publisher Nature Portfolio
publishDate 2019
url https://doaj.org/article/90d7b523d73d42dd8591096c779df15c
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