Prognostic significance of NF-κB expression in non-small cell lung cancer: A meta-analysis

Gu, Lijun; Wang, Zhiyan; Zuo, Jing; Li, Hongmei; Zha, Lin

doi:10.1371/journal.pone.0198223

Cited by 41 publications

(34 citation statements)

References 34 publications

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“…In addition, NF-κB provides one important linkage between the pathogenesis of pulmonary inflammation and cancer [124]. In this line, a recent meta-analysis [125] showed that NF-κB-positive lung cancer cells (analyzed by immunohistochemistry) are highly significantly correlated with shorter overall survival time. This might be true for both canonical and non-canonical NF-κB signaling pathways [126,127].…”

Section: Lung Cancer and Cancer Stem Cellsmentioning

confidence: 99%

A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells

Kaltschmidt

Banz‐Jansen

Benhidjeb³

et al. 2019

Cancers

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Cancer stem cells (CSCs) account for tumor initiation, invasiveness, metastasis, and recurrence in a broad range of human cancers. Although being a key player in cancer development and progression by stimulating proliferation and metastasis and preventing apoptosis, the role of the transcription factor NF-κB in cancer stem cells is still underestimated. In the present review, we will evaluate the role of NF-κB in CSCs of glioblastoma multiforme, ovarian cancer, multiple myeloma, lung cancer, colon cancer, prostate cancer, as well as cancer of the bone. Next to summarizing current knowledge regarding the presence and contribution of CSCs to the respective types of cancer, we will emphasize NF-κB-mediated signaling pathways directly involved in maintaining characteristics of cancer stem cells associated to tumor progression. Here, we will also focus on the status of NF-κB-activity predominantly in CSC populations and the tumor mass. Genetic alterations leading to NF-κB activity in glioblastoma, ependymoma, and multiple myeloma will be discussed.

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Section: Lung Cancer and Cancer Stem Cellsmentioning

confidence: 99%

A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells

Kaltschmidt

Banz‐Jansen

Benhidjeb³

et al. 2019

Cancers

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“…Specially, this CSC characteristics, namely 'stemness', can be highly induced by chronic exposure to TNF-α combined with TGF-β 16, which is tightly involved by NF-κB signaling in cytokine production and immune responses. Recent discovery demonstrate NF-κB significantly involve the capability of CSCs 17 and is highly associated with poor survival in NSCLC 18. FoxM1 is a member of the forked box transcription factor family, which has been widely reported in regulating the stemness of CSC 19 and cause progression in tumorigenesis 20.…”

Section: Introductionmentioning

confidence: 99%

8-bromo-7-methoxychrysin targets NF-κB and FoxM1 to inhibit lung cancer stem cells induced by pro-inflammatory factors

Yuan¹,

Wen²,

Xu³

et al. 2019

J. Cancer

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We have previously reported that 8-bromo-7-methoxychrysin (BrMC), a novel synthetic derivative of chrysin, was demonstrated anti-tumor activities against several human cancers, including lung cancer. Interaction between inflammation and cancer stem cell are recently increasingly recognized in tumorigenesis and progression. The purpose of this study was to investigate whether BrMC inhibits lung cancer stemness of H460 cells induced by inflammatory factors (TGF-β combined with TNF-α) and its potential mechanism. Our results showed that BrMC inhibited lung cancer stemness, as validated by enhanced self-renewal ability, higher in vitro tumorigenicity, and increased expression of CD133, CD44, Bmi1 and Oct4 in H460 cells administered TNF-α after prolonged induction by TGF-β, in a concentration-dependent manner. Both NF-κB inhibition by SN50 and FoxM1 suppression by thiostrepton (THI) prompted the inhibition of BrMC on lung CSCs. Conversely, overexpression of NF-κBp65 significantly antagonized the above effects of BrMC. Meanwhile, overexpression of FoxM1 also significantly compromised BrMC function on suppression of FoxM1 and NF-κBp65 as well as stemness of lung CSCs. Our results suggest that activation of NF-κB and FoxM1 by cytokines facilitate the acquisition CSCs phenotype, and compromise the chemical inhibition, which may represent an effective therapeutic target for treatment of human lung cancer. Moreover, BrMC may be a potential promising candidate for targeting NF-κB/ FoxM1 to prevent the tumorigenesis under inflammatory microenvironment.

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“…The involvement of the alternative pathway of NF-κΒ has been increasingly recognized in lung cancer initiation, progression and clinical outcome as well as in response to treatment 17,20 . We have demonstrated previously that NF-κΒ2 and RelB are overexpressed in non-small-cell carcinomas 17 .…”

Section: Discussionmentioning

confidence: 99%

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

Dimitrakopoulos

Antonacopoulou

Κοττόρου

et al. 2019

Sci Rep

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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.

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Prognostic significance of NF-κB expression in non-small cell lung cancer: A meta-analysis

Cited by 41 publications

References 34 publications

A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells

A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells

8-bromo-7-methoxychrysin targets NF-κB and FoxM1 to inhibit lung cancer stem cells induced by pro-inflammatory factors

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

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