scholarly journals Clinicopathological significance of DAPK gene promoter hypermethylation in non-small cell lung cancer: A meta-analysis

2021 ◽  
pp. 172460082110675
Author(s):  
Zhimao Chen ◽  
Yu Fan ◽  
Xiangzheng Liu ◽  
Xueqian Shang ◽  
Kang Qi ◽  
...  

Background Death-associated protein kinase (DAPK) has a strong function of tumor suppression involving apoptosis regulation, autophagy, and metastasis inhibition. Hypermethylation of CpG islands in DAPK gene promoter region is one of the important ways to inactivate this tumor suppressor gene, which might promote lung carcinogenesis. However, the clinicopathological significance of the DAPK promoter hypermethylation in lung cancer remains unclear. In this study, we performed a meta-analysis trying to estimate the clinicopathological significance of DAPK promoter hypermethylation in non-small cell lung cancer (NSCLC). Methods A detailed literature search for publications relevant to DAPK gene promoter methylation and NSCLC was made in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, CSTJ, Wanfang databases, and SinoMed (CBM). The random-effects model and fixed-effects model were utilized to pool the relative ratio based on the heterogeneity test in the meta-analysis. Results A total of 41 studies with 3348 patients were included. The frequency of DAPK methylation was significantly higher in NSCLC than in non-malignant control (odds ratio (OR) = 6.88, 95% confidence interval (CI):  4.17–11.35, P < 0.00001). The pooled results also showed that DAPK gene promoter hypermethylation was significantly associated with poor prognosis for overall survival in patients with NSCLC (hazard ratio: 1.23, 95% CI:1.01–1.52, P = 0.04). Moreover, DAPK gene promoter hypermethylation was significantly associated with squamous cell carcinoma (OR: 1.25, 95% CI: 1.01–1.54, P = 0.04) and smoking behavior (OR: 1.42, 95% CI: 1.04–1.93, P = 0.03) but not with TNM stage, tumor differentiation, age, or gender. Conclusion DAPK promoter hypermethylation might be a candidate diagnostic and prognostic tumor marker for NSCLC.

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Xin Hua ◽  
Jing Chen ◽  
Ying Wu ◽  
Jun Sha ◽  
Shuhua Han ◽  
...  

Abstract Background Inflammation plays a critical role in the development and progression of cancers. The advanced lung cancer inflammation index (ALI) is thought to be able to reflect systemic inflammation better than current biomarkers. However, the prognostic significance of the ALI in various types of cancer remains unclear. Our meta-analysis aimed to comprehensively investigate the relationship between the ALI and oncologic outcomes to help physicians better assess the prognosis of cancer patients. Methods The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched for relevant studies. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated and pooled from the included studies. Furthermore, a sensitivity analysis was performed to evaluate the reliability of the articles. Finally, Begg’s test, Egger’s test, and the funnel plot were applied to assess the significance of publication bias. Results In total, 1736 patients from nine studies were included in our meta-analysis. The median cutoff value for the ALI was 23.2 (range, 15.5–37.66) in the analyzed studies. The meta-analysis showed that there was a statistically significant relationship between a low ALI and worse overall survival (OS) in various types of cancer (HR = 1.70, 95% CI = 1.41–1.99, P < 0.001). Moreover, results from subgroup meta-analysis showed that the ALI had a significant prognostic value in non-small cell lung cancer, small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, and diffuse large B cell lymphoma (P < 0.05 for all). Conclusions These results showed that a low ALI was associated with poor OS in various types of cancer, and the ALI could act as an effective prognostic biomarker in cancer 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.


2021 ◽  
Author(s):  
Yong Li ◽  
Fang Yang ◽  
Ya-Yong Huang ◽  
Tao Wang

Abstract BackgroundStage I non-small-cell lung cancer (NSCLC) can be treated by both ablation and sublobar resection (SR). This meta-analysis was therefore designed to better compare the relative safety and efficacy of these two approaches to treating stage I NSCLC.Materials and MethodsRelevant studies published through November 2020 in the Cochrane Library, Embase, and PubMed databases were identified for analyses which were conducted with RevMan v5.3. ResultsIn total, 816 potentially relevant articles were identified, of which 8 were ultimately included in the final meta-analysis. Patients in the SR group exhibited a signficantly lower pooled local recurrence (LR) rate (5.0% vs. 25.4%, P < 0.0001), although pooled distant recurrence (DR) rates were similar in both groups (25.7% vs. 23.1%, P = 0.75). The pooled hazard ratio (HR) for overall survival (OS) (HR: 1.23; 95% CI: 1.13-1.33, P < 0.00001), progression-free survival (PFS) (HR: 1.34; 95% CI: 1.15-1.55, P = 0.0002), and cancer-specific survival (CSS) (HR: 1.39; 95% CI: 1.15-1.70, P = 0.0009) all indicated better survival outcomes among patients that underwent HR treatment, while pooled complication rates were similar in both groups (27.7% vs. 43.8%, P = 0.27). Patients that underwent ablation exhibited significantly shorter pooled post-operative hospitalization relative to those in the SR group (MD: 5.93; 95% CI: 0.78-11.07, P = 0.02). No evidence of publication bias was detected through funnel plot analyses.ConclusionsSR treatment of stage I NSCLC patients was associated with a lower LR rate and longer survival as compared to ablation.


2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Shi ◽  
Shuai Zhu ◽  
Hengjuan Guo ◽  
Xiongfei Li ◽  
Shikang Zhao ◽  
...  

IntroductionPrevious studies have demonstrated that programmed cell death-ligand 1 (PD-L1) serves as biomarker for poor prognosis and survival in advanced-stage non-small cell lung cancer (NSCLC) patients. However, the merit of PD-L1 expression to predict the prognosis of early stage NSCLC patients who underwent complete resection remains controversial. In the present study, we performed a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in patients with early stage resected NSCLC.MethodsElectronic databases, including PubMed, EMBASE, and the Cochrane Library, were searched until July 23 2020 for studies evaluating the expression of PD-L1 and the prognosis of resected NSCLCs. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and disease-free survival (DFS) were pooled and analyzed. Heterogeneity and publication bias analyses were also assessed.ResultsA total of 15 studies involving 3,790 patients were considered in the present meta-analysis. The pooled HR indicated that PD-L1 expression related to a much shorter DFS (HR = 1.56, 95% CI: 1.18–2.05, p &lt; 0.01), as well a significantly worse OS (HR = 1.68, 95% CI: 1.29–2.18, p &lt; 0.01). Furthermore, our analysis indicated that PD-L1 expression was significantly associated with gender (male vs. female: OR = 1.27, 95% CI:1.01–1.59, p = 0.038), histology (ADC vs. SCC: OR = 0.54, 95% CI:0.38–0.77, p = 0.001), TNM stage (I vs. II–III: OR = 0.45, 95% CI:0.34–0.60, p = 0.000), smoking status (Yes vs No: OR = 1.43, 95% CI:1.14–1.80, p = 0.002) and lymph node metastasis (N+ vs N−: OR = 1.97, 95% CI:1.26–3.08, p = 0.003).ConclusionsThe results of this meta-analysis suggest that PD-L1 expression predicts an unfavorable prognosis in early stage resected NSCLCs. The role of personalized anti-PD-L1/PD-1 immunotherapy in the adjuvant settings of resected NSCLC warrants further investigation.


2020 ◽  
Vol 9 (4) ◽  
pp. 1063 ◽  
Author(s):  
Tung Hoang ◽  
Seung-Kwon Myung ◽  
Thu Thi Pham ◽  
Jeongseon Kim ◽  
Woong Ju

This study aims to investigate the efficacy of targeted therapies in the treatment of non-small cell lung cancer (NSCLC) by using a network meta-analysis of clinical trials. PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov were searched by using keywords related to the topic on 19 September 2018. Two investigators independently selected relevant trials by pre-determined criteria. A pooled response ratio (RR) for overall response rate (ORR) and a hazard ratio (HR) for progression-free survival (PFS) were calculated based on both the Bayesian and frequentist approaches. A total of 128 clinical trials with 39,501 participants were included in the final analysis of 14 therapeutic groups. Compared with chemotherapy, both ORR and PFS were significantly improved for afatinib, alectinib, and crizotinib, while only PFS was significantly improved for cabozantinib, ceritinib, gefitinib, and osimertinib. Consistency was observed between the direct and indirect comparisons based on the Bayesian approach statistically and the frequentist approach visually. Cabozantinib and alectinib showed the highest probability for the first-line treatment ranking in ORR (62.5%) and PFS (87.5%), respectively. The current network meta-analysis showed the comprehensive evidence-based comparative efficacy of different types of targeted therapies, which would help clinicians use targeted therapies in clinical practice.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Weibo Wen ◽  
Yongnan Piao ◽  
Dongyuan Xu ◽  
Xiangdan Li

Purpose. The present systematic literature review and meta-analysis focused on examining the significance of total lesion glycolysis (TLG) and metabolic tumor volume (MTV) in predicting the prognosis of stages I/II non-small-cell lung cancer (NSCLC) based on 18F-FDG PET parameters. Methods. Electronic databases, including Cochrane Library, PubMed, and EMBASE, were comprehensively searched for retrieving relevant articles published in the English language. Furthermore, the significance of TLG and MTV in prognosis prediction was analyzed by pooled hazard ratios (HRs). Results. This work enrolled eight primary studies with 1292 I/II-stage NSCLC cases. The pooled HR (95% confidence interval [CI]) for the ability of increased TLG to predict progression-free survival (PFS) was 2.02 (1.30–2.13) ( P = 0.350 ), while for increased MTV it was 3.04 (1.92–4.81) ( P = 0.793 ). In addition, the pooled HR (95% CI) for the ability of increased TLG to predict overall survival (OS) was 2.16 (1.49–3.14) ( P = 0.624 ). However, higher MTV correlated with OS, and sensitivity analysis showed that the results were not stable. Multivariate and univariate analyses by subgroup analyses stratified by PFS of MTV and OS of TLG exhibited statistically significant differences, without any statistical heterogeneity across various articles. Conclusion. The present work suggests the predictive value of PET/CT among stage I and II NSCLC patients. Our results verified that stage I/II NSCLC cases with increased TLG and MTV had a higher risk of side reactions, and TLG is related to increased mortality risk.


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