Prognostic and clinicopathological significance of tertiary lymphoid structure in non-small cell lung cancer: a systematic review and meta-analysis
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ABSTRACT:
SUBMITTER: Ma L
PROVIDER: S-EPMC11229181 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC7665804 | biostudies-literature
Project description:BackgroundEpithelial cadherin (E-cadherin), a calcium-dependent cell-cell adhesion molecule, as an important adhesion and signaling pathway mediator plays key roles in the maintenance of tissue integrity. However, the available results of E-cadherin expression and its prognostic value on non-small cell lung cancer (NSCLC) remain controversial. Therefore, a meta-analysis of published studies investigating the prognostic value of E-cadherin expression and its association with clinicopathological characteristics with NSCLC was performed.MethodsA literature search via PubMed, EMBASE, and MEDLINE (Ovid) databases was conducted. Data from eligible studies were extracted. Statistical analysis was performed using STATA 12.0.ResultsA total of 2412 patients from 15 studies were included in the meta-analysis. The results showed that the pooled hazard ratio (HR) for overall survival was 0.55 (95% confidence interval [CI]: 0.44-0.69) by univariate analysis and 0.68 (95% CI: 0.43-1.08) by multivariate analysis. In addition, the results showed a significant association between E-cadherin expression and the presence of lymph node metastasis (odds ratio = 0.37, 95% CI=0.05-0.69, P = 0.001).ConclusionOur study showed that positive expression of E-cadherin was associated with a favorable prognosis in patients with NSCLC, and might act as an inhibition factor of metastasis. However, adequately designed prospective studies are required to confirm this finding.
| S-EPMC4567004 | biostudies-literature
Project description:BackgroundMany studies have investigated the prognostic role of E-cadherin in patients with NSCLC; however, the result still remains inconclusive. An up-to data system review and meta-analysis was necessary to give a comprehensive evaluation of prognostic role of E-cadherin in NSCLC.MethodsEligible studies were searched in Pubmed, Embase and Web of Science databases. The inclusion criteria were studies that assessed the relationship between E-cadherin expression detected by immunohistochemistry (IHC) and the prognosis or clinicopathological features in patients with NSCLC. Subgroup analysis according to race, percentage of reduced/negative E-cadherin expression, histological type, and sample size were also conducted. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to examine the risk or hazard association.ResultsA total of 29 studies including 4010 patients were qualified for analysis. The analysis suggested that downregulated E-cadherin expression was significant associated with unfavorable overall survival (OS) and disease-free survival/progression-free survival (DFS/PFS) in patients with NSCLC. Subgroup analysis by race, percentage of reduced/negative E-cadherin expression, sample size also found the significant association in OS. When only the stage I NSCLC were considered, downregulated E-cadherin expression still had an unfavorable impact on OS. Additionally, downregulated E-cadherin expression was significantly associated with differentiation grade, lymphnode metastasis, vascular invasion, and TNM stage.ConclusionDownregulated E-cadherin expression detected by IHC seems to correlate with tumour progression and could serve as an important prognostic factor in patients with NSCLC.
| S-EPMC4076188 | biostudies-literature
Project description:This study aimed to understand the clinicopathological significance of runt-related transcription factor 1 (RUNX1) in non-small cell lung cancer (NSCLC). The methylation and mRNA levels of RUNX1 in NSCLC were determined using the Infinium HumanMethylation450 BeadChip and the HumanHT-12 expression BeadChip. RUNX1 protein levels were analyzed using immunohistochemistry of formalin-fixed paraffin-embedded tissues from 409 NSCLC patients. Three CpGs (cg04228935, cg11498607, and cg05000748) in the CpG island of RUNX1 showed significantly different methylation levels (Bonferroni corrected p < 0.05) between tumor and matched normal tissues obtained from 42 NSCLC patients. Methylation levels of the CpGs in the tumor tissues were inversely related to mRNA levels of RUNX1. A logistic regression model based on cg04228935 showed the best performance in predicting NSCLCs in a test dataset (N = 28) with the area under the receiver operating characteristic (ROC) curve (AUC) of 0.96 (95% confidence interval (CI) = 0.81-0.99). The expression of RUNX1 was reduced in 125 (31%) of 409 patients. Adenocarcinoma patients with reduced RUNX1 expression showed 1.97-fold (95% confidence interval = 1.16-3.44, p = 0.01) higher hazard ratio for death than those without. In conclusion, the present study suggests that abnormal methylation of RUNX1 may be a valuable biomarker for detection of NSCLC regardless of race. And, reduced RUNX1 expression may be a prognostic indicator of poor overall survival in lung adenocarcinoma.
| S-EPMC7356912 | biostudies-literature
Project description:Various studies examined the relationship between EZH2 overexpression with the clinical outcome in patients with non-small cell lung cancer (NSCLC), but yielded inconsistent results. Electronic databases updated to Dec 2014 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between EZH2 overexpression and survival of patients with NSCLC Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 10 studies (n = 1,695 patients) that evaluated the correlation between EZH2 overexpression and survival in patients with lung cancer. Combined hazard ratios suggested that EZH2 overexpression was associated with poor prognosis of overall survival (OS) (HR = 1.68, 95% CI: 1.42-1.93) in patients with lung cancer. In the stratified analysis, significantly risks were found among Asians (HR = 1.33, 95% CI: 1.62-1.70), lung adenocarcinoma patients (HR = 1.75, 95% CI: 1.38-2.52, in stage I NSCLC patients (HR = 2.51, 95% CI: 1.23-3.79), but not among Caucasians. EZH2 overexpression indicates a poor prognosis for patients with NSCLC, this effect appears also significant when the analysis is restricted in Asian population, lung AC and stage I patients, but not among Caucasians.
| S-EPMC4709684 | biostudies-other
Project description:BackgroundLung adenocarcinoma (LUAD) is a highly mortal cancer. Tertiary lymphoid structures (TLS) are ectopic lymphoid organs with similar morphological and molecular characters to secondary lymphoid organ. The aim of this study is to investigate the prognostic effect of a gene signature associated with TLSs, including B-cell-specific genes.MethodsClinical data of 515 LUAD patients in the TGCA cohort were used to examine the relationship of TLS signature with immune microenvironment, tumor mutational burden (TMB), and driver gene mutations. Patients were divided into the TLS signature high group and TLS signature low group, and comparative analysis of survival and its influencing factors between the two groups was performed. The resulting data were then validated in the GSE37745 cohort.ResultsTLS signature high group had significantly better overall survival (OS) and progression-free interval (PFI) as well as significantly higher infiltration of immune cell subsets, cancer immune cycle (CIC) signature except for immunogram score2 (IGS2), and expression of major checkpoint genes than the TLS signature low group. Notably, while TLS signature was not markedly associated with TMB and mutation frequencies of driver genes, there were significant differences in overall survival of patients with given mutation status of EGFR, KRAS, BRAF and TP53 genes between the TLS signature high and low groups.ConclusionThis study provided evidence that LUAD patients with high TLS signature had a favorable immune microenvironment and better prognosis, suggesting that TLS signature is an independent positive prognostic factor for LUAD patients.
| S-EPMC8352557 | biostudies-literature
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.
| S-EPMC7556468 | biostudies-literature
Project description:BackgroundTumor-associated immune cells are prognostic in non-small cell lung cancer (NSCLC) but findings have been conflicting.ObjectivesTo determine the prognostic role of immune cells according to localization in NSCLC patients.MethodsA systematic literature review and meta-analysis was performed on dendritic cell (DC), tumor associated macrophages (TAM), mast cells (MC), natural killer (NK) cells, T and B cells and tumor CTLA-4 and PD-L1 studies.ResultsWe analysed 96 articles (n= 21,752 patients). Improved outcomes were seen with increased tumor DCs (overall survival (OS) hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.44-0.68), NK cells (OS HR 0.45; 0.31-0.65), TAMs (OS HR 0.33; 0.17-0.62), M1 TAMs (OS HR 0.10; 0.05-0.21), CD3+ T cells (disease specific survival (DSS) HR 0.64; 0.48-0.86), CD8+ T cells (OS HR 0.78; 0.66-0.93), B cells (OS HR 0.65; 0.42-0.99) and with increased stroma DC (DSS HR 0.62; 0.47-0.83), NK cells (DSS HR 0.51; 0.32-0.82), M1 TAMs (OS HR 0.63; 0.42-0.94), CD4+ T cells (OS HR 0.45; 0.21-0.94), CD8+ T cells (OS HR 0.77; 0.69-0.86) and B cells (OS HR 0.74;0.56-0.99). Poor outcomes were seen with stromal M2 TAMs (OS HR 1.44; 1.06-1.96) and Tregs (relapse free survival (RFS) HR 1.80; 1.34-2.43). Tumor PD-L1 was associated with worse OS (1.40; 1.20-1.69), RFS (1.67) and DFS (1.24).ConclusionTumor and stroma DC, NK cells, M1 TAMs, CD8+ T cells and B cells were associated with improved prognosis and tumor PD-L1, stromal M2 TAMs and Treg cells had poorer prognosis. Higher quality studies are required for confirmation.
| S-EPMC5973851 | biostudies-literature
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.
| S-EPMC9271448 | biostudies-literature
Project description:Emerging evidence indicates that FHIT is a candidate tumor suppressor in non-small cell lung cancer (NSCLC). However, the correlation between FHIT hypermethylation and clinicopathological characteristics of NSCLC remains unclear. Thus, we conducted a meta-analysis to quantitatively evaluate the effects of FHIT hypermethylation on the incidence of NSCLC and clinicopathological characteristics. Final analysis of 1717 NSCLC patients from 16 eligible studies was performed. FHIT hypermethylation was found to be significantly higher in NSCLC than in normal lung tissue, the pooled OR from 8 studies including 735 NSCLC and 708 normal lung tissue, OR = 5.45, 95% CI = 2.15-13.79, p = 0.0003. FHIT hypermethylation was also correlated with sex status, smoking status, as well as pathological types. We did not find that FHIT hypermethylation was correlated with the differentiated types or clinical stages in NSCLC patients. However, patients with FHIT hypermethylation had a lower survival rate than those without, HR = 1.73, 95% CI = 1.10-2.71, p = 0.02. The results of this meta-analysis suggest that FHIT hypermethylation is associated with an increased risk and worsen survival in NSCLC patients. FHIT hypermethylation, which induces the inactivation of FHIT gene, plays an important role in the carcinogenesis and clinical outcome and may serve as a potential drug target of NSCLC.
| S-EPMC4726317 | biostudies-other