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

Date Published: May 29, 2018

Publisher: Public Library of Science

Author(s): Lijun Gu, Zhiyan Wang, Jing Zuo, Hongmei Li, Lin Zha, Kenneth B. Marcu.

http://doi.org/10.1371/journal.pone.0198223

Abstract

Nuclear factor kappa B (NF-κB), a key nuclear transcription factor, is associated with prognosis in a variety of human cancers. However, the clinical value of NF-κB in non-small cell lung cancer (NSCLC) is still controversial. Therefore, the aim of this meta-analysis was to obtain an accurate evaluation of the relationship between NF-κB expression and survival prognosis of NSCLC patients based on published articles. PubMed, EMBASE and Web of Science databases were systematically searched for potential articles. A total of 1159 patients from 7 eligible studies comparing prognostic significance of NF-κB expression levels in NSCLC were included in our meta-analysis. I2 statistic and P value were performed to evaluate heterogeneity. The results of analysis were presented as hazard ratio (HR) or odds ratios (OR) with 95% confidence interval (95% CI). Subgroup analysis based on ethnicity of NSCLC patients and NF-kB cellular localization within cancer cells were conducted to illustrate the potential discrepancy. Significant heterogeneity was considered at I2>50% and P<0.05, and random-effects model was used. The combined results indicated that higher NF-κB expression was associated with shorter overall survival (OS) of NSCLC patients (HR = 2.78, 95% CI = 1.51–5.12, P = 0.001). Moreover, NF-κB expression was closely associated with tumor stage (HR = 0.32, 95% CI = 0.18–0.57, P<0.0001), lymph node metastasis (HR = 0.56, 95% CI = 0.38–0.83, P = 0.004) and 5-year OS for NSCLC patients (OR = 1.83, 95% CI = 1.02–3.31, P = 0.04). We conclude that NF-κB expression may be a potential unfavorable prognostic marker for NSCLC patients.

Partial Text

Non-small cell lung cancer (NSCLC) is a major cause of cancer mortality and is one of the most common cancers worldwide [1]. In spite of recent advances in treatment including targeted therapy, adjuvant therapy and surgery, the overall prognosis of NSCLC is grim and the 5-year survival rate is as low as 15% [2, 3]. Therefore, a more favorable prognostic biomarker that contributes to the improvement of survival situation is crucial for the development of therapeutic strategies against NSCLC.

It has been documented that NF-κB, an important inflammatory transcriptional factor, performs a pivotal part in various biological processes and has a dual effect on the progression of cancers [22, 23]. Some researchers have identified high expression levels of NF-κB in variety of solid malignancies, such as breast cancer, renal cell carcinoma and oral squamous cell carcinoma [24–26]. Inhibitors targeting at NF-κB expression also inhibited the tumor formation and angiogenesis capacity of lung cancer cells [27]. On the contrary, some studies have shown that NF-κB transactivated the expression of pro-apoptosis genes including Fas and death receptors, and NF-κB performed as a tumor suppressor to facilitate P53-related cancer cell death [28–30]. Therefore, NF-κB may act as different roles in diverse types of carcinoma. As to the prognosis of NSCLC, the relationship of NF-κB expression with survival outcome remains uncertain. Previous studies have reported that NSCLC patients are characterized by enhanced NF-κB expression. However, other studies have demonstrated reduced level of NF-κB expression observed in NSCLC cells. Understanding the prognostic value of NF-κB in NSCLC patients may provide insights for the improvement of clinical outcome. Therefore, our meta-analysis exploring the prognostic role of NF-κB in NSCLC patients is clinically significant.

 

Source:

http://doi.org/10.1371/journal.pone.0198223

 

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