Bioinformatics and experimental approach identify lipocalin 2 as a diagnostic and prognostic indicator for lung adenocarcinoma.

BACKGROUND: lipocalin 2 (LCN2) is a secreted glycoprotein that plays key roles in tumorigenesis and progression. Interestingly, LCN2 appears to have a contradictory function in developing lung adenocarcinoma (LUAD). Thus, we intend to explore the role of LCN2 in LUAD through bioinformatics and experimental validation. METHODS: LCN2 expression of LUAD was investigated in the TCGA, TIMER and HPA databases. The relationship between LCN2 and prognosis was investigated by KM plotter, TCGA and GEO databases. GO, KEGG and protein-protein interactions network analysis were conducted to investigate the potential mechanism of LCN2. The relevance of LCN2 to cancer-immune infiltrates was investigated in the TCGA and TIMER databases. Quantitative reverse transcription PCR, western blot and enzyme-linked immunosorbent assay were performed to identify the expression level of LCN2 in cells and serum samples. The CCK-8, wound healing and transwell assay were used to confirm the effect of LCN2 on cell proliferation, migration and invasion in LUAD. The receiver operating characteristic curve was utilized to assess the diagnostic efficiency of LCN2 further. RESULTS: LCN2 expression was significantly upregulated in LUAD (P < 0.05), and was correlated with the clinical stage, tumor size, lymph node metastasis and distant metastasis (P < 0.05). There was a high correlation between high LCN2 and worse prognosis in LUAD. Functional network analysis suggested that LCN2 was associated with multiple signal pathways in cancers, such as JAK-STAT, TNF, NF-κB, HIF-1 and PI3K-Akt signal pathways. In addition, the knockdown of LCN2 significantly inhibited the ability of cell proliferation, migration and invasion. Immune infiltration analysis indicated that LCN2 is associated with multiple immune cell infiltration. Notably, LCN2 demonstrated high diagnostic efficiency for LUAD (AUC = 0.818, P < 0.05), especially for stage III-IV patients could reach 0.895. CONCLUSIONS: LCN2 as an oncogenic glycoprotein promotes the cancer progression related to immune infiltrates, which might be a potential diagnostic and prognostic marker in LUAD.

MECOM: a bioinformatics and experimentally identified marker for the diagnosis and prognosis of lung adenocarcinoma.

Objective: We aimed to explore the clinical value of MDS1 and EVI1 complex locus (MECOM) in lung adenocarcinoma (LUAD). Methods: Bioinformatics and experimental validation confirmed MECOM expression levels in LUAD. The value of MECOM was analyzed by receiver operating characteristic (ROC) curve and Cox regression analysis. Results: Serum MECOM levels were lower in LUAD and correlated with gender, TNM stage, tumor size, lymph node metastasis and distant metastasis. The ROC curve showed that the area under the curve of MECOM was 0.804 for LUAD and, of note, could reach 0.889 for advanced LUAD; specificity was up to 90%. Conclusion: MECOM may contribute to independently identifying LUAD patients, particularly in advanced stages.

Lung adenocarcinoma is a common type of lung cancer with a high incidence and death rate. However, clinical indicators that effectively identify lung adenocarcinoma patients are still lacking. The protein encoded by the MECOM gene is a DNA-binding protein regulating gene expression, which has been found to play a cancer-promoting role in many cancers, but we found that it may play a cancer-suppressing role in lung adenocarcinoma. This study aimed to confirm whether MECOM can be a predictor for lung adenocarcinoma. Our results showed that lung adenocarcinoma patients had lower serum MECOM levels than healthy people, and patients with lower MECOM levels had a shorter survival rate. That is, patients with lower serum MECOM levels may indicate a high risk of developing lung adenocarcinoma and death. Thus, the MECOM gene is expected to be a predictor associated with the risk of developing lung adenocarcinoma and death.

Association of antihypertensive drugs with COVID-19 outcomes: a drug-target Mendelian randomization study.

Background: Observational investigations have provided conflicting results regarding the effect of antihypertensive drugs on the risk of COVID-19 outcomes. We intended to assess the causal effect of antihypertensive drugs on COVID-19 outcomes using drug-target Mendelian randomization (MR), mainly including angiotensin-converting enzyme inhibitors (ACEIs), ß-blockers (BBs) and calcium channel blockers (CCBs). Methods: We used the genetic variants (minor allele frequency >1%, r 2 < 0.30) located within 100 k bases of each drug target gene and associated with lower systolic blood pressure (p < 5 × 10-8) as genetic proxies for antihypertensive drugs. COVID-19 outcomes included COVID-19 susceptibility (122,616 cases and 2,475,240 controls), hospitalization (32,519 cases and 206,2805 controls), and severe illness (13,769 cases and 1,072,442 controls). All studies were conducted on populations of European ancestry. MR estimates were generated using an inverse variance weighted (IVW) model. Results: IVW-MR analysis observed a weak causality between CCBs and COVID-19 susceptibility (OR: 0.993, 95% CI: 0.988-0.999, p = 0.012). Sensitivity analysis suggested that this result was robust. No evidence was found for a link between other antihypertensive drugs and COVID-19 outcomes. Conclusion: The present study suggests that CCBs may reduce COVID-19 susceptibility in European populations.

Clinicopathological characteristics correlated with programmed cell death-ligand 1 expression in advanced lung adenocarcinoma.

Background: Recent studies have shown that immune checkpoint inhibitors (ICIs) targeting programmed cell death-ligand 1 (PD-L1) have potential benefits in patients with non-small cell lung cancer (NSCLC) subgroups, while the clinicopathological characteristics associated with PD-L1 expression have not been well established. The purpose of this study was to detect the expression level of PD-L1 in tumor tissues of patients with advanced lung adenocarcinoma (ADC) and analyze its possible relationship with clinicopathological characteristics, so as to identify the predictors of PD-L1 expression. Methods: This retrospective study was conducted by analyzing the clinicopathological and imaging characteristics of hospitalized advanced lung ADC patients with PD-L1 available data and admitted to the respiratory department of our hospital. The expression level of PD-L1 in fresh-frozen tumor tissue samples of 136 advanced ADC patients was analyzed by immunohistochemistry. The patients were divided into positive and negative groups based on a cut-off of 1% PD-L1 expression level. Subsequently, the significant correlation between PD-L1 levels and clinicopathological features were evaluated. The predictive performance of clinicopathological characteristics on PD-L1 expression was evaluated and the optimal cut-off values were identified by plotting the receiver operating characteristic (ROC) curve. Results: The expression level of PD-L1 was related to sex, clinical stage, serum carcinoembryonic antigen (CEA), neuron specific enolase (NSE), white blood cell (WBC), and tumor (T) and metastasis (M) stage. Multivariate logistic regression analysis showed the CEA, NSE, T stage, and WBC were independent predictors of PD-L1 positive expression in lung ADC patients. The ROC curve suggested the model combining CEA with NSE [area under the curve (AUC) =0.815] could better predict the expression levels of PD-L1. The optimal cut-off values for identifying advanced lung ADC patients with PD-L1 positive were CEA ≤13.38 ng/mL and NSE ≤42.35 ng/mL, with sensitivity and specificity of 85.4% and 55.6%, and 92.7% and 32.1%, respectively. Conclusions: Some commonly used clinicopathological features are related to the histological expression of PD-L1. The serum CEA, NSE, T stage, and WBC values can be used as indicators to predict the expression level of PD-L1 in advanced lung ADC, and are used as predictors to evaluate the efficacy of ICIs before treatment.

High blood urea nitrogen to creatinine ratio is associated with increased risk of sarcopenia in patients with chronic obstructive pulmonary disease.

BACKGROUND AND AIMS: Sarcopenia has been reported to be a prognostic factor for chronic obstructive pulmonary disease (COPD). However, the relationship between the ratio of blood urea nitrogen to creatinine (BUN/Cr) and sarcopenia in patients with COPD remain unclear. Therefore, the purpose of this study is to explore whether the ratio can be used as a predictor of sarcopenia in hospitalized COPD patients. METHODS: The skeletal muscle area index (SMI) at the level of the 12th thoracic vertebra (T12) was used to assess the risk of sarcopenia in patients. This single center cross-sectional study was conducted by analyzing the clinical parameters and identifying the T12 skeletal muscle area (SMA) and density (SMD) on chest CT images of COPD hospitalized patients admitted to the respiratory department of our hospital from March 2018 to August 2021. The study enrolled 265 hospitalized patients. Based on the different statistical properties of the above variables, differences between groups were measured by independent sample Student t-tests, Mann-Whitney U tests, or Chi-Square tests. Multivariable linear regression analysis was used to evaluate the relationship between the value of BUN/Cr and the risk of sarcopenia. RESULTS: The serum BUN/Cr ratio was negatively correlated with SMI (r = -0.201, p = 0.001) in COPD patients, and multivariate linear regression analysis showed that this ratio was associated with the risk of sarcopenia (ß = -0.109, p = 0.041). The optimal cut-off value of BUN/Cr ratio for identifying COPD patients with sarcopenia was 97.893. There was also a significant negative correlation between serum BUN/Cr ratio and forced vital capacity (FVC; r = -0.235, p < 0.001) and forced expiratory volume in the first second (FEV1; r = -0.219, p < 0.001). CONCLUSION: The BUN/Cr ratio can be used to predict sarcopenia and evaluate pulmonary function in hospitalized COPD patients.

Genetic susceptibility to COVID-19 may increase the risk of erectile dysfunction: A two-sample Mendelian randomization study.

Coronavirus disease 19 (COVID-19) and erectile dysfunction (ED) have been linked in some observational research, but the causality of this association in the European population is uncertain. Therefore, the research intended to investigate the causality of susceptibility to COVID-19 on ED. We used Mendelian randomization (MR) analysis for this research. The subjects were from two genome-wide association studies (GWAS) of the European population, including COVID-19 (14,134 cases and 1,284,876 controls) and ED (6175 cases and 217,630 controls). We utilized the inverse variance-weighted (IVW) to evaluate the causality of COVID-19 genetic susceptibility on ED. Heterogeneity and pleiotropy were determined using the Cochran's Q test and MR-Egger regression. The robustness of the findings was verified using the Leave-one-out method. We obtained six single nucleotide polymorphisms (SNPs) as COVID-19 genetic instrumental variables (IVs), and there was no significant pleiotropy, heterogeneity or bias in these IVs. MR analysis revealed the causality of genetic susceptibility to COVID-19 on elevated risk of ED (ORIVW  = 1.235, 95% CI: 1.044-1.462, p < 0.05). The present study suggested the causality of genetic susceptibility to COVID-19 on elevated ED risk among the European population. Therefore, in order to decrease the ED risk, the European population ought to positively prevent COVID-19.

A primary Ewing's sarcoma of pleura: Case report and literature review.

Ewing's sarcoma was first reported by J.Ewing in 1921, which is generally originated from soft tissue of the trunk or limbs. Primary Extraskeletal Ewing sarcoma (EES) of pleura is an uncommon condition, which is challenging to diagnose, and rarely reported. Herein, we present a previously 14-year-old male patient with fever and dyspnea for 1 month presented to the department of respiratory medicine in Binzhou Medical University Hospital. Radiology revealed a soft mass with massive pleural effusion in the right side of pleural cavity. After admission, we performed the transthoracic catheter drainage for the patient, followed by thoracoscopy and biopsy. Histopathology revealed a small round cell malignant tumor, combined with immunohistochemistry assay and the Fluorescence in-situ hybridization (FISH) detection of EWSR1 gene arrangement, Ewing's sarcoma was finally diagnosed. Despite receiving chemo- and radiotherapy, the patient died 1 year later after diagnosis. This paper reports a rare case that originated in parietal pleura with massive pleural effusion of Ewing's sarcoma, which was not previously reported. This rare tumor and its unusual clinical manifestations prompt us to report the current case.

Carcinoma ex pleomorphic adenoma of the trachea: A case report.

BACKGROUND: Carcinoma ex pleomorphic adenoma (CXPA) is defined as a malignant salivary gland tumor arising from a primary or recurrent pleomorphic adenoma. Only three cases of CXPA of the trachea have been reported in the literature. CASE SUMMARY: We report a case of tracheal CXPA in a 55-year-old woman, who presented with a more than 3-mo history of progressive dyspnea. Computed tomography of the neck and thorax revealed an inhomogeneous, broad-based lesion arising from the tracheal wall on the right side. Endoscopy revealed a subglottic neoplasm causing up to 90% luminal stenosis. The tumor was resected using a high-frequency electrosurgical snare combined with argon plasma coagulation. Histopathology and immunohistochemistry revealed that the tumor was a CXPA of the trachea. CONCLUSION: We report the fourth case of tracheal CXPA, and present the first instance of resection of CXPA using high-frequency electrosurgical snare and laser ablation. We also discuss the pathogenesis, diagnosis, histopathology, and systemic therapy of this rare disease.