Pterostilbene pre-treatment reduces LPS-induced acute lung injury through activating NR4A1.

CONTEXT: Pterostilbene (PTE), a common polyphenol compound, exerts an anti-inflammatory effect in many diseases, including acute lung injury (ALI). OBJECTIVE: This study explores the potential mechanism of PTE pre-treatment against lipopolysaccharide (LPS)-induced ALI. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were divided into control, ALI, 10 mg/kg PTE + LPS, 20 mg/kg PTE + LPS, and 40 mg/kg PTE + LPS groups. At 24 h before LPS instillation, PTE was administered orally. At 2 h before LPS instillation, PTE was again administered orally. After 24 h of LPS treatment, the rats were euthanized. The levels of inflammatory cells and inflammatory factors in the bronchoalveolar lavage fluid (BALF), the expression of nuclear receptor subfamily 4 group A member 1 (NR4A1), and the nuclear factor (NF)-κB pathway-related protein levels were detected. NR4A1 agonist was used to further investigate the mechanism of PTE pre-treatment. RESULTS: After PTE pre-treatment, the LPS induced inflammation was controlled and the survival rate was increased to 100% from 70% after LPS treatment 24 h. For lung injury score, it decreased to 1.5 from 3.5 after treating 40 mg/kg PTE. Compared with the control group, the expression of NR4A1 in the ALI group was decreased by 20-40%. However, the 40 mg/kg PTE pre-treatment increased the NR4A1 expression by 20-40% in the lung tissue. The results obtained with pre-treatment NR4A1 agonist were similar to those obtained by pre-treatment 40 mg/kg PTE. CONCLUSIONS: PTE pre-treatment might represent an appropriate therapeutic target and strategy for preventing ALI induced by LPS.

Systemic immune-inflammation index predicting chemoradiation resistance and poor outcome in patients with stage III non-small cell lung cancer.

BACKGROUND: There is increasing evidence that the existence of systemic inflammation response is correlated with poor prognosis in several solid tumors. The aim of this retrospective study was to investigate the association between systemic immune-inflammation index (SII) and therapy response and overall survival in patients with stage III non-small cell lung cancer (NSCLC). The prognostic values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were also evaluated. METHODS: In total, 332 patients with new diagnosis of stage III NSCLC were included in this retrospective analysis. SII was defined as platelet counts × neutrophil counts/lymphocyte counts. Receiver operating characteristic (ROC) curve was used to evaluate the optimal cut-off value for SII, NLR, PLR and PNI. Univariate and multivariate survival analysis were performed to identify the factors correlated with overall survival. RESULTS: Applying cut-offs of ≥ 660 (SII), ≥ 3.57 (NLR), ≥ 147 (PLR), ≤ 52.95 (PNI), SII ≥ 660 was significantly correlated with worse ECOG PS (< 0.001), higher T stage (< 0.001), advanced clinical stage (p = 0.019), and lower response rate (p = 0.018). In univariate analysis, SII ≥ 660, NLR ≥ 3.57, PLR ≥ 147, and PNI ≤ 52.95 were significantly associated with worse overall survival (p all < 0.001). Patients with SII ≥ 660 had a median overall survival of 10 months, and patients with SII < 660 showed a median overall survival of 30 months. In multivariate analysis only ECOG PS (HR, 1.744; 95% CI 1.158-2.626; p = 0.008), T stage (HR, 1.332; 95% CI 1.032-1.718; p = 0.028), N stage (HR, 1.848; 95% CI 1.113-3.068; p = 0.018), SII (HR, 2.105; 95% CI 1.481-2.741; p < 0.001) and NLR ≥ 3.57 (HR, 1.934; 95% CI 1.448-2.585; p < 0.001) were independently correlated with overall survival. CONCLUSIONS: This study demonstrates that the SII is an independent prognostic indicator of poor outcomes for patients with stage III NSCLC and is superior to other inflammation-based factors in terms of prognostic ability.

Lymphocyte to monocyte ratio is associated with response to first-line platinum-based chemotherapy and prognosis of early-stage non-small cell lung cancer patients.

Lymphocyte to monocyte ratio (LMR) has shown prognostic value in different types of cancer. This study assessed the prognostic performance of LMR in early-stage non-small cell lung cancer (NSCLC) patients and investigated the influence of LMR on the treatment response in patients receiving first-line platinum-based chemotherapy. Four hundred eighty-eight NSCLC patients and 500 healthy donors were enrolled in this study. The cutoff value for LMR was chosen by receiver operating characteristic curve analysis. The prognostic significance of markers was assessed by univariate and multivariate Cox regression models. The median overall survival was 43 months, and the median progression-free survival was 38 months. LMR was associated with disease status and the treatment response of first-line platinum-based chemotherapy. Multivariate analysis showed that LMR was an independent prognostic factor for both overall survival (hazard ratio = 1.53, 95 % confidence interval = 1.09-2.14, P = 0.015) and progression-free survival (hazard ratio = 1.20, 95 % confidence interval = 1.02-1.67, P = 0.028). Furthermore, integration of LMR into a prognostic model including TNM stage, tumor status, chemotherapy, and histological type generated a nomogram, which predicted accurately overall survival for NSCLC patients. Decreased LMR may be a potential biomarker of disease status, worse response to first-line platinum-based chemotherapy, and worse survival for NSCLC patients. A prospective study is warranted for further validation of our findings.

Integrated analysis reveals key genes with prognostic value in lung adenocarcinoma.

BACKGROUND: Lung cancer is one of the most common malignant tumors. Despite advances in lung cancer therapies, prognosis of non-small-cell lung cancer is still unfavorable. The aim of this study was to identify the prognostic value of key genes in lung tumorigenesis. METHODS: Differentially expressed genes (DEGs) were screened out by GEO2R from three Gene Expression Omnibus cohorts. Common DEGs were selected for Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology enrichment analysis. Protein- protein interaction networks were constructed by the STRING database and visualized by Cytoscape software. Hub genes, filtered from the CytoHubba, were validated using the Gene Expression Profiling Interactive Analysis database, and their genomic alterations were identified by performing the cBioportal. Finally, overall survival analysis of hub genes was performed using Kaplan-Meier Plotter. RESULTS: From three datasets, 169 DEGs (70 upregulated and 99 downregulated) were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that upregulated DEGs were significantly enriched in cell cycle, p53 pathway, and extracellular matrix-receptor interactions; the downregulated DEGs were significantly enriched in PPAR pathway and tyrosine metabolism. The protein-protein interaction network consisted of 71 nodes and 305 edges, including 49 upregulated and 22 downregulated genes. The hub genes, including AURKB, BUB1B, KIF2C, HMMR, CENPF, and CENPU, were overexpressed compared with the normal group by Gene Expression Profiling Interactive Analysis analysis, and associated with reduced overall survival in lung cancer patients. In the genomic alterations analysis, two hotspot mutations (S2021C/F and E314K/V) were identified in Pfam protein domains. CONCLUSION: DEGs, including AURKB, BUB1B, KIF2C, HMMR, CENPF, and CENPU, might be potential biomarkers for the prognosis and treatment of lung adenocarcinoma.

Direct bilirubin levels are prognostic in non-small cell lung cancer.

We investigated the prognostic value of serum bilirubin levels in stage I-II non-small cell lung cancer (NSCLC) patients and evaluated the relationship between bilirubin levels and response to first-line platinum-based chemotherapy. We divided 634 NSCLC patients from a single hospital in China into retrospective training (n = 307) and prospective validation (n = 327) cohorts. X-tile was used to identify the optimal serum bilirubin cutoff value for sorting retrospective cohort patients into low and high overall survival (OS) groups. TNM stage and serum bilirubin levels were associated with OS on univariate analysis. Direct bilirubin (DBIL) levels were correlated with tumor progression and response to first-line platinum-based chemotherapy, and were associated with OS after adjusting for TNM stage. Our findings indicate a DBIL-based prognostic nomogram is more accurate than the TNM staging system in predicting clinical outcomes, and that the DBIL level is an independent predictor of OS in NSCLC. Thus, an index that combines DBIL with TNM stage may better predict patient outcomes than TNM stage alone.

Combination of long noncoding RNA MALAT1 and carcinoembryonic antigen for the diagnosis of malignant pleural effusion caused by lung cancer.

PURPOSE: Long noncoding RNAs (lncRNAs) are present in body fluids, but their potential as tumor biomarkers has never been investigated in malignant pleural effusion (MPE) caused by lung cancer. The aim of this study was to assess the clinical significance of lncRNAs in pleural effusion, which could potentially serve as diagnostic and predictive markers for lung cancer-associated MPE (LC-MPE). PATIENTS AND METHODS: RNAs from pleural effusion were extracted in 217 cases of LC-MPE and 132 cases of benign pleural effusion (BPE). Thirty-one lung cancer-associated lncRNAs were measured using quantitative real-time polymerase chain reaction (qRT-PCR). The level of carcinoembryonic antigen (CEA) was also determined. The receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were established to evaluate the sensitivity and specificity of the identified lncRNAs and other biomarkers. The correlations between baseline pleural effusion lncRNAs expression and response to chemotherapy were also analyzed. RESULTS: Three lncRNAs (MALAT1, H19, and CUDR) were found to have potential as diagnostic markers in LC-MPE. The AUCs for MALAT1, H19, CUDR, and CEA were 0.891, 0.783, 0.824, and 0.826, respectively. Using a logistic model, the combination of MALAT1 and CEA (AUC, 0.924) provided higher sensitivity and accuracy in predicting LC-MPE than CEA (AUC, 0.826) alone. Moreover, baseline MALAT1 expression in pleural fluid was inversely correlated with chemotherapy response in patients with LC-MPE. CONCLUSION: Pleural effusion lncRNAs were effective in differentiating LC-MPE from BPE. The combination of MALAT1 and CEA was more effective for LC-MPE diagnosis.