Nitric oxide in occurrence, progress and therapy of lung Cancer: a systemic review and meta-analysis.

BACKGROUND: Nitric oxide (NO) plays an important role in lung cancer. However, the results of previous studies about NO in the occurrence, progress and therapy were not consistent. Therefore, we conducted a meta-analysis to evaluate the relationship between NO and lung cancer. METHOD: We carried out comprehensive search in the databases, and collected related studies. The data of fraction of exhaled nitric oxide (FeNO) or blood NO in different populations (lung cancer patients and control subjects) and different time points (before therapy and after therapy) were extracted by two investigators. A random effect model was applied to analyze the differences of FeNO and blood NO in different populations and different time points. To further compare NO level of each subgroup with different pathological types and different stages, a network meta-analysis (NMA) was performed. RESULTS: Fifty studies including 2551 cases and 1691 controls were adopted in this meta-analysis. The FeNO (SMD 3.01, 95% CI 1.89-4.13, p < 0.00001) and blood NO (SMD 1.34, 95% CI 0.84-1.85, p < 0.00001) level in lung cancer patients was much higher than that in control subjects. NMA model indicated blood NO level in each cancer type except SCLC was higher than that in control patients. There was no significant difference of blood NO level among four kinds of lung cancer patients. Blood NO level in LCC patients (SUCRA = 83.5%) was the highest. Blood NO level in advanced stage but not early stage was higher than that in control subjects. Patients in advanced stage (SUCRA = 95.5%) had the highest blood NO level. No significant difference of FeNO (SMD -0.04, 95% CI -0.46-0.38, p > 0.05) and blood NO level (SMD -0.36, 95% CI -1.08-0.36, p > 0.05) was observed between pretreatment and posttreatment in all patients. However, FeNO level elevated (SMD 0.28, 95% CI 0.04-0.51, p = 0.02) and blood NO level decreased in NSCLC patients (SMD -0.95, 95% CI -1.89-0.00, p = 0.05) after therapy. CONCLUSION: FeNO and blood NO level would contribute to diagnosis of lung cancer and evaluation of therapy effect, especially for NSCLC patients.

Genetic polymorphism of heme oxygenase 1 promoter in the occurrence and severity of chronic obstructive pulmonary disease: a meta-analysis.

Heme oxygenase 1 (HMOX1) plays an important role in the development of chronic obstructive pulmonary disease (COPD). However, the association of HMOX1 length polymorphism in promoter region to the risk and severity of COPD has not been well studied. In this study, we searched the databases including PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI) and extracted the information from related articles. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to study the effect of HMOX1 polymorphism on the risk and severity of COPD. As a result, nine studies were included for this meta-analysis. Higher frequencies of L allele and type I genotype (containing at least one L allele) were found in patients with COPD (for L allele, OR 2.02, 95% CI: 1.32-3.11, P = 0.001; for type I genotype, OR 1.82, 95% CI: 1.28-2.61, P = 0.001), especially in Asian population (for L allele, OR 2.23, 95% CI: 1.68-2.95, P < 0.001; for type I genotype, OR 2.02, 95% CI: 1.51-2.70, P < 0.001). Genotyping method, source of control subjects, literature quality and language also affected the results to some extent. However, there was little difference in HMOX1 genotypes distribution in patients with COPD with different severity. Our study indicated L allele and type I genotype were related to the susceptibility but not the severity of COPD.

Platelet-lymphocyte ratio is a prognostic marker in small cell lung cancer-A systemic review and meta-analysis.

Aim: The aim of this study was to evaluate the relationship between platelet-lymphocyte ratio (PLR) and prognosis in small cell lung cancer (SCLC) patients. Method: A comprehensive search was carried out to collect related studies. Two independent investigators extracted the data of hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) or progression-free survival (PFS). A random-effect model was applied to analyze the effect of different PLR levels on OS and PFS in SCLC patients. Moreover, subgroup analysis was conducted to seek out the source of heterogeneity. Results: A total of 26 articles containing 5,592 SCLC patients were included for this meta-analysis. SCLC patients with a high PLR level had a shorter OS compared with patients with a low PLR level, in both univariate (HR = 1.56, 95% CI 1.28-1.90, p < 0.0001) and multivariate (HR = 1.31, 95% CI 1.08-1.59, p = 0.007) models. SCLC patients with a high PLR level had a shorter PFS compared with patients with a low PLR level, in the univariate model (HR = 1.71, 95% CI 1.35-2.16, p < 0.0001), but not in the multivariate model (HR = 1.17, 95% CI 0.95-1.45, p = 0.14). Subgroup analysis showed that a high level of PLR shortened OS in some subgroups, including the Asian subgroup, the younger subgroup, the mixed-stage subgroup, the chemotherapy-dominant subgroup, the high-cutoff-point subgroup, and the retrospective subgroup. PLR level did not affect OS in other subgroups. Conclusion: PLR was a good predictor for prognosis of SCLC patients, especially in patients received chemotherapy dominant treatments and predicting OS. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022383069.

Crizotinib changes the metabolic pattern and inhibits ATP production in A549 non-small cell lung cancer cells.

Crizotinib, an inhibitor of the hepatocyte growth factor receptor oncogene, has been studied extensively regarding its antitumor and clinically beneficial effects in non-small cell lung cancer (NSCLC). However, crizotinib's effects on cancer cell energy metabolism, which is linked with tumor proliferation and migration, in NSCLC are unclear. Therefore, the present study focused on crizotinib's effect on NSCLC glucose metabolism. Crizotinib's effects on glucose metabolism, proliferation, migration and apoptosis in A549 cells were explored. Several other inhibitors, including 2-DG, rotenone and MG132, were used to define the mechanism of action in further detail. Data showed that crizotinib treatment reduced A549 cell viability, increased glucose consumption and lactate production, while decreased mitochondrial transmembrane potential (Δψm) and ATP production. Crizotinib treatment, combined with rotenone and MG132 treatment, further inhibited ATP production and Δψm and increased reactive oxygen species content. However, crizotinib did not suppress cell proliferation, migration, ATP production, Δψm or mitochondrial-related apoptosis signals further following 2-DG-mediated inhibition of glycolysis. These results indicated that crizotinib induced low mitochondrial function and compensatory high anaerobic metabolism, but failed to maintain sufficient ATP levels. The alternation of metabolic pattern and insufficient ATP supply may serve important roles in the metabolic antitumor mechanism of crizotinib in A549 cells.

The Efficacy and Risk Profile of c-Met inhibitors in Non-small Cell Lung Cancer: a Meta-analysis.

c-MET inhibitors are considered as a kind of novel drugs in non-small cell lung cancer (NSCLC) treatment. However, the results of different clinical studies involving c-MET inhibitors were not consistent. In this report, we performed Meta-analysis to investigate the beneficial and harmful effects of these drugs from 9 studies including 1611 patients in target drug groups and 1605 patients in control groups. As a result, patients in target drugs group had longer progression free survival (PFS) (HR 0.80, 95% CI 0.66-0.99, p = 0.04) but not overall survival (OS) than those in control group, especially in Asian (HR 0.57, 95% CI 0.42-0.76, p < 0.001), Non-squamous (HR 0.79, 95% CI 0.64-0.97, p = 0.03), Phase III (HR 0.66, 95% CI 0.50-0.86, p = 0.002), previous treated (HR 0.77, 95% CI 0.63-0.95, p = 0.01) and small molecular compounds subgroups (HR 0.62, 95% CI 0.50-0.78, p < 0.001). In addition, target drugs did not affect the objective response rate (ORR) but improved disease control rate (DCR) (RR 1.22, 95% CI 1.02-1.46, p = 0.03) of NSCLC patients. Our study first indicated that targeting c-MET therapies improved PFS and DCR in advanced or metastatic NSCLC patients, especially in previous treated Asian patients with adenocarcinoma.