scholarly journals Prognostic and clinicopathological significance of NRF2 expression in non-small cell lung cancer: A meta-analysis

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241241
Author(s):  
Qingsong Wang ◽  
Liang Xu ◽  
Gang Wang ◽  
Lei Chen ◽  
Changping Li ◽  
...  

Nuclear factor erythroid 2-related factor 2 (NRF2) functions as a transcription factor and regulates a wide array of antioxidant and stress-responsive genes. NRF2 has been widely implicated in different types of cancers, but only limited studies concerning the relationship between NRF2 expression and tumour invasion or prognosis in lung cancer. Therefore, we conducted a meta-analysis to determine the prognostic value of NRF2 in patients with non-small cell lung cancer (NSCLC). The relationship between NRF2 expression in NSCLC patients and clinicopathological features was also investigated. Overall survival (OS) and treatment response rate were evaluated using STATA software. Twenty eligible articles with 2530 lung cancer patients were included in this meta-analysis. The results revealed that high expression level of NRF2 was associated with pathologic distant metastasis (odds ratio (OR) = 2.64, 95% confidence interval (CI) 1.62–4.31; P < 0.001), lymph node metastasis (OR = 2.14, 95% CI: 1.53–3.00; P < 0.001), and tumour node metastasis (TNM) stage (OR = 1.95, 95% CI: 1.52–2.49, P < 0.001). High NRF2 expression was associated with low treatment response rate in platinum-based chemotherapy (HR = 0.11, 95% CI 0.02–0.51; P = 0.005). High expression level of NRF2 is predictive for poor overall survival rate (HR = 1.86, 95% CI 1.44–2.41, P < 0.001) and poor progression-free survival (PFS) (HR = 2.27, 95% CI 1.26–4.09, P = 0.006). Compared to patients with a low level of NRF2 expression, patients with high NRF2 expression levels were associated with worse OS and PFS when given the chemotherapy or EGFR-TKI. Together, our meta-analysis results suggest that NRF2 can act as a potential indicator of NSCLC tumour aggressiveness and help the prognosis and design of a better treatment strategy for NSCLC patients.

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenhua Zhao ◽  
Wei Jiang ◽  
Huilin Wang ◽  
Jianbo He ◽  
Cuiyun Su ◽  
...  

ObjectivesTo evaluate the impact of smoking history on the clinical benefit of immunotherapy in patients with non-small cell lung cancer (NSCLC).MethodsTwenty-three randomized clinical trials and seven real-world studies were included in this meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) and odds ratios for the overall response rate (ORR) were extracted. A fixed-effects or random-effects model was applied to obtain pooled estimates.ResultsData from 16 high-quality trials involving 10,643 NSCLC patients receiving either immunotherapy or chemotherapy/placebo enabled direct comparison of the survival impact of smoking. Anti-PD-1/PD-L1/CTLA-4 immunotherapy was found to significantly prolong OS and PFS as compared to chemotherapy/placebo in smokers (HR for OS, 0.76 [0.69–0.83], P&lt;0.00001; HR for PFS, 0.65 [0.56–0.75], P&lt;0.00001), and these trends were less or not significant in non-smokers (HR for OS, 0.91 [0.78–1.06], P=0.25; HR for PFS, 0.68 [0.45–1.03], P=0.07). Consistent results were obtained for the first-line or second/third-line use of immunotherapy and for non-squamous NSCLC patients only. Furthermore, the data from 7 trials and 7 real-world studies involving 4,777 patients receiving immunotherapy allowed direct comparison of therapeutic outcomes between smokers and non-smokers. Prolonged OS (HR 0.86 [0.75–0.99], P=0.04) and PFS (HR 0.69 [0.60–0.81], P&lt;0.0001) and a higher response rate (ORR 1.20 [0.94–1.53], P=0.15) were observed in smokers compared to non-smokers receiving immunotherapy.ConclusionsImmunotherapy was found to have a greater benefit in NSCLC patients with a smoking history than in those who had never smoked.


2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Jing Zhang ◽  
Yanhui Gu ◽  
Xiaoli Liu ◽  
Ximin Rao ◽  
Guichuan Huang ◽  
...  

Abstract Background: Numerous published studies have shown that S100A4 is frequently overexpressed in various human cancers. However, the association between S100A4 expression and prognosis or clinicopathological parameters in non-small cell lung cancer (NSCLC) remains unclear. Therefore, a meta-analysis was performed to identify the significance of S100A4 in NSCLC. Methods: Systematic literature search was conducted using PubMed, Embase, Web of Science, the Cochrane Library, the Chinese National Knowledge Infrastructure database (CNKI), and the Wanfang database to obtain relevant articles. A combined hazard ratio (HR) and its corresponding 95% confidence interval (CI) were used to evaluate the association between S100A4 expression and prognosis in NSCLC patients. Pooled odds ratio (OR) and 95% CI were calculated to assess the association between S100A4 expression and clinicopathological features in NSCLC. Results: NSCLC patients with overexpression of S100A4 had a worse prognosis than patients with low expression of S100A4 (HR = 1.77, 95% CI: 1.55–2.02, P&lt;0.001). Additionally, overexpression of S100A4 was significantly correlated to patients’ age (OR = 0.67, 95% CI: 0.49–0.91, P=0.010), tumor differentiation (OR = 2.20, 95% CI: 1.69–2.85, P&lt;0.001), lymph node metastasis (LNM) (OR = 3.70, 95% CI: 2.25–6.06, P&lt;0.001), Tumor-Node-Metastasis (TNM) stage (OR = 3.08, 95% CI: 2.10–4.53, P&lt;0.001), and pathological subtype (OR = 1.77, 95% CI: 1.09–2.88, P=0.020). However, there was no association between S100A4 expression and other clinicopathological features in NSCLC, including gender, tumor size, and smoking. Conclusion: S100A4 overexpression was associated with tumor progression and poor prognosis in NSCLC patients. Hence, S100A4 might serve as a potential prognostic biomarker in NSCLC.


2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Zhichao Wang ◽  
Fanchao Feng ◽  
Qi Wu ◽  
Yihan Jin ◽  
Cheng Gu ◽  
...  

Purpose. Disodium cantharidinate and vitamin B6 (DCVB6) injection is effective and widely used for the clinical treatment of non-small-cell lung cancer (NSCLC). This meta-analysis aimed to provide evidence-based medical data for clinical treatment with DCVB6 injection. Methods. We searched 7 medical databases up to January 2018 for all randomized controlled trials (RCTs) based on DCVB6 injection combined with chemotherapy in patients with NSCLC. A manual search in relevant journals and of relevant literature on other websites was also performed. Data extraction and quality assessment were conducted independently by two reviewers. Subsequently, a meta-analysis was conducted using RevMan 5.3 software. Pooled risk ratio (RR) with 95% confidence interval (CI) was used to evaluate dichotomous and continuous outcomes, respectively. The PROSPERO ID was CRD42018086377. Results. A total of 19 RCTs were included. The results of the meta-analysis indicated that the DCVB6 injection combined with chemotherapy was superior to chemotherapy alone regarding objective response rate (RR=1.58, 95% CI 1.40-1.79), Karnofsky performance score (RR=1.68, 95% CI 1.42-1.99), clinical symptom (RR=1.68, 95% CI 1.44-1.96), white blood cell toxicity (RR=0.36, 95% CI 0.27-0.49), platelet toxicity (RR=0.46, 95% CI 0.33-0.63), and vomiting (RR=0.50, 95% CI 0.37-0.67). Conclusions. The current evidence suggests that DCVB6 injection combined with chemotherapy could increase objective response rate and Karnofsky performance score, improve clinical symptoms, and reduce side effects caused by chemotherapy in patients with NSCLC. However, these results should be carefully interpreted due to the low-quality methodology and the small sample sizes of the trials, and our conclusions should be verified by high-quality, large-scale, double-blinded RCTs.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Sunyin Rao ◽  
Lianhua Ye ◽  
Li Min ◽  
Guangqiang Zhao ◽  
Ya Chen ◽  
...  

Abstract Objective Whether segmentectomy can be used to treat radiologically determined pure solid or solid-dominant lung cancer remains controversial owing to the invasive pathologic characteristics of these tumors despite their small size. This meta-analysis compared the oncologic outcomes after lobectomy and segmentectomy regarding relapse-free survival (RFS) and overall survival (OS) in patients with radiologically determined pure solid or solid-dominant clinical stage IA non-small cell lung cancer (NSCLC). Methods A literature search was performed in the MEDLINE, EMBASE, and Cochrane Central databases for information from the date of database inception to March 2019. Studies were selected according to predefined eligibility criteria. The hazard ratio (HR) and associated 95% confidence interval (CI) were extracted or calculated as the outcome measure for data combining. Results Seven eligible studies published between 2014 and 2018 enrolling 1428 patients were included in the current meta-analysis. Compared with lobectomy, segmentectomy had a significant benefit on the RFS of radiologically determined pure solid or solid-dominant clinical stage IA NSCLC patients (combined HR: 1.46; 95% CI, 1.05–2.03; P = 0.024) and there were no significant differences on the OS of these patients (HR: 1.52; 95% CI, 0.95–2.43; P = 0.08). Conclusions Segmentectomy leads to lower survival than lobectomy for clinical stage IA NSCLC patients with radiologically determined pure solid or solid-dominant tumors. Moreover, applying lobectomy to clinical stage IA NSCLC patients with radiologically determined pure solid or solid-dominant tumors (≤2 cm) could lead to an even bigger survival advantage. However, there are some limitations in the present study, and more evidence is needed to support the conclusion.


2016 ◽  
Vol 11 (1) ◽  
pp. 220-224
Author(s):  
Chongwei Wang ◽  
Chongbang Wang ◽  
Shufang Duan

AbstractObjectives: As the member of the Fox family of transcription factors, Forkhead box M1 (FoxM1) is known to be critical in pathogenesis and development of many solid tumors. However, the clinical value and expression pattern in non-small cell lung cancer (NSCLC) is still poorly understood. Methods: In this study, real-time PCR was mainly applied to examine the gene expression levels of FoxM1 in 120 pairs of clinical NSCLC tissues, which were classified into different groups according to smoking status, lymph node metastasis, and tumor grade. By utilizing the online Kaplan-Meier plotter, overall survival analysis was performed to study the correlation between FoxM1 expression and prognosis of lung cancer (LC) patients. Afterwards, the correlation of FoxM1 gene expression and the clinical pathological parameters was examined by κ2 test in these 120 NSCLC patients. Results: FoxM1 was found to be aberrantly upregulated in NSCLC patients, and its overexpression was correlated to groups designated as smokers, cases of positive lymph node metastasis and cases of advanced tumor grades. Online survival analysis showed that high expression of FoxM1 predicted shorter overall survival of NSCLC patients. Additionally, FoxM1 upregulation was statistically correlated with positive smoking history, lymph node metastasis and higher tumor grades. Conclusion: FoxM1 is overexpressed in cancerous tissues and is associated with the poor prognosis of NSCLC patients. Our results provide insights into the utility of FoxM1 as an important biomarker and prognostic factor for NSCLC.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Yu Shi ◽  
Jianxin Yang ◽  
Ninghua Yao ◽  
Minghai Shao ◽  
Wenxiu Ding ◽  
...  

Background. The aim was to investigate the potential factors related with overall survival of oligometastatic non-small-cell lung cancer (NSCLC) patients. Methods. A literature search was conducted in databases including PubMed, Embase, and Cochrane library up to March 2017. The hazard radio (HR) as well as the corresponding 95% confidence interval (CI) were calculated, and all the statistics analysis was performed by the R 3.12. Heterogeneity was analyzed using I-squared and Cochran Q tests. Furthermore, sensitivity analysis was performed to evaluate the stability of results. Results. In total, 6 articles were included in the meta-analysis. Nodal status was significantly correlated with the overall survival rate of NSCLC oligometastatic patients (HR: 1.69, 95% CI: 1.23–2.32, Z=3.20, P=0.001). No significant relationship was found between overall survival rate of NSCLC oligometastatic patients and the indicators including sex, stage, smoker, age, and histology. Notably, sensitivity analysis on data evaluating relationship between patients survival and the stage and histology showed that results were reversed after removing one of the studies. Conclusions. Nodal status might be associated with the overall survival of oligometastatic NSCLC patients.


2018 ◽  
Vol 8 (9) ◽  
pp. 1875-1880
Author(s):  
Jiang Rui ◽  
Li Yingping ◽  
Lijun Gu ◽  
Zhiyan Wang ◽  
Jing Zuo ◽  
...  

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 using Review Manager version 5.3. The results of analysis were presented as hazard ratio (HR) or odds ratios with 95% confidence interval (95% CI). Subgroup analysis based on ethnicity of NSCLC patients was 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 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) and lymph node metastasis (HR = 0.56, 95% CI = 0.38–0.83, P = 0.004). We conclude that NF-κB expression may be a potential unfavorable prognostic marker for NSCLC patients.


2020 ◽  
Author(s):  
Yu Bai ◽  
Xu Ma ◽  
Sen Han ◽  
Jian Fang

Abstract Background: Patients with non-small cell lung cancer (NSCLC) have a significantly higher risk of developing venous thromboembolism (VTE), a condition that significantly influences the prognosis of these patients. However, the impact of VTE on the survival of NSCLC patients remains unclear. We aim to evaluate the impact of VTE on the mortality of patients with NSCLC. Methods: We systematically reviewed all indexed studies examining the prognosis of NSCLC patients with VTE. Web of Science, EMBASE, PubMed, and the Cochrane Library were searched through December 31, 2019 to identify relevant studies. Fixed- or random-effects models were chosen based on heterogeneity. Results: Twelve articles with 6480 patients were included in this analysis. The heterogeneity of these studies was significant (I2=81%, P<0.01). The overall survival (OS) of NSCLC patients with VTE was shorter compared to patients without VTE (HR=1.71, 95% CI [1.39–2.10], P<0.01). Two small groups of SCLC patients were excluded and the remaining patients were divided into the Asian and non-Asian groups. The Asian group showed low heterogeneity (I2=35%, P=0.20), in which NSCLC patients with VTE also had shorter OS (HR=1.49, 95% CI [1.19–1.88], P<0.01). Conclusions: VTE is significantly associated with a shorter OS of NSCLC patients, especially in Asian patients. Proper prevention and management of VTE is the key to improving the survival of patients with NSCLC.


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