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

ABSTRACT: 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.

SUBMITTER: Wang Q

PROVIDER: S-EPMC7665804 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Wang Qingsong Q Xu Liang L Wang Gang G Chen Lei L Li Changping C Jiang Xiangli X Gao Hai H Yang Bing B Tian Weiping W

PloS one 20201113 11

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 b ...[more]

PMID: 33186371

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Project description:BackgroundAlthough expression of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) in tumor tissues has been assessed in several malignancies. However, the association between lncRNA MALAT-1 expression and prognosis or clinicopathological feature remains controversial. Therefore, we conducted a meta-analysis to verify whether lncRNA MALAT-1 expression was associated with prognosis or clinicopathological features in patients with non-small cell lung cancer (NSCLC).MethodsWe searched Embase, PubMed, Web of Science, Cochrane library, The Chinese National Knowledge Infrastructure, and Wanfang databases from inception to March, 1, 2020. The language restrictions were Chinese and English. The published literature on lncRNA MALAT-l expression and prognosis or clinicopathological characteristics of NSCLC patients was statistically analyzed. Combined hazard ratios (HRs), odds ratios (OR), and 95% confidence intervals (95% CIs) were used to evaluate the effects of lncRNA MALAT-l on the prognosis and clinicopathological features of NSCLC.ResultsFifteen studies with 1477 NSCLC patients were enrolled. The results showed that the elevated expression of lncRNA MALAT-l in tumor tissues was associated with shorter overall survival (OS) (HR: 2.20, 95% CI: 1.53-3.16; P = 0.000). Additionally, high lncRNA MALAT-l expression was also significantly associated with gender (OR: 0.69, 95% CI: 0.51-0.93; P = 0.014), tumor size (OR: 1.87, 95% CI:1.13-3.09; P = 0.016), lymph node metastasis (LNM) (OR: 2.87, 95% CI:1.05-7.83, P = 0.04), tumor differentiation (OR: 1.60, 95% CI:1.17-2.20; P = 0.003), and tumor-node-metastasis (TNM) stage (OR: 0.42, 95% CI: 0.25-0.70; P = 0.001). There was no significant relationship between lncRNA MALAT-l expression and other clinicopathological features including age (OR: 1.03, 95% CI: 0.79-1.34; P = 0.830), number of tumors (OR: 1.02, 95% CI: 0.63-1.64; P = 0.943), vascular invasion (OR: 1.23, 95% CI: 0.50-3.05; P = 0.652), and recurrence (OR: 1.98, 95% CI: 0.67-5.85; P = 0.214).ConclusionThe overexpression of lncRNA MALAT-l in NSCLC tissues was correlated with OS, gender, tumor size, LNM, tumor differentiation, and TNM stage. Thus, lncRNA MALAT-l may serve as a prognostic factor for NSCLC.

Project description:BackgroundAlthough the prognosis of non-small cell lung cancer (NSCLC) can be assessed based on pathological type, disease stage and inflammatory indicators, the prognostic scoring model of NSCLC still needs to improve. HDAC11 is associated with poor prognosis of partial tumors, but its prognostic relationship with NSCLC is poorly understood. In this study, the role of HDAC11 in NSCLC was studied to evaluate relationship with disease prognosis and potential therapeutic target.MethodsThe clinicopathological and paracancerous tissues of patients with NSCLC primarily diagnosed in Tangdu Hospital from 2009 to 2013 were collected. Follow-up of patients were made every three months and the last follow-up period was December 2018. The expression of HDAC11 was assessed by immunohistochemistry (IHC). Then, weighted gene co-expression network analysis (WGCNA) was used to analyze the relationship between HDAC11 expression and the prognosis of lung adenocarcinoma (LUAD) patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Kaplan-Meier plotter database was used to verify the connection between hub genes and tumor stage and prognosis. We accessed the relationship between HDAC11 expression and clinicopathological features, and impact on the prognosis.ResultsThe study assessed 326 patients with NSCLC. Compared with adjacent tissues, HDAC11 expression was upregulated (HR =1.503, 95% CI: 1.172 to 1.927, P=0.001). Kaplan-Meier survival analyses showed that HDAC11 expression was closely related to OS of NSCLC patients (P=0.0011). Univariate and multivariate analyses showed that the independent risk factors of OS were clinical stage, HDAC11 expression, and HDAC11 differentiation (all P≤0.001). HDAC11 was significantly associated with prognosis in LUAD. A total of 1,174 differential genes and WGCNA were obtained to construct a co-expression network in LUAD. The GO and KEGG pathway enrichment analyses showed the relevance with staphylococcus aureus infection, NOD-like receptor signaling pathway, and others. The results of LUAD survival analysis showed that HDAC11-related genes NKX2-5 and FABP7 were significantly associated with LUAD prognosis.ConclusionsThe high expression of HDAC11 is related to the poor prognosis of LUAD, and it is expected to become a therapeutic target and prognostic evaluation therapy for LUAD in the future. However, the relevant results need to be further studied and verified.

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Dataset Information

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

Publications

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

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