Identification of three hub genes related to the prognosis of idiopathic pulmonary fibrosis using bioinformatics analysis.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic respiratory disease characterized by peripheral distribution of bilateral pulmonary fibrosis that is more pronounced at the base. IPF has a short median survival time and a poor prognosis. Therefore, it is necessary to identify effective prognostic indicators to guide the treatment of patients with IPF. Methods: We downloaded microarray data of bronchoalveolar lavage cells from the Gene Expression Omnibus (GEO), containing 176 IPF patients and 20 controls. The top 5,000 genes in the median absolute deviation were classified into different color modules using weighted gene co-expression network analysis (WGCNA), and the modules significantly associated with both survival time and survival status were identified as prognostic modules. We used Lasso Cox regression and multivariate Cox regression to search for hub genes related to prognosis from the differentially expressed genes (DEGs) in the prognostic modules and constructed a risk model and nomogram accordingly. Moreover, based on the risk model, we divided IPF patients into high-risk and low-risk groups to determine the biological functions and immune cell subtypes associated with the prognosis of IPF using gene set enrichment analysis and immune cell infiltration analysis. Results: A total of 153 DEGs located in the prognostic modules, three (TPST1, MRVI1, and TM4SF1) of which were eventually defined as prognostic hub genes. A risk model was constructed based on the expression levels of the three hub genes, and the accuracy of the model was evaluated using time-dependent receiver operating characteristic (ROC) curves. The areas under the curve for 1-, 2-, and 3-year survival rates were 0.862, 0.885, and 0.833, respectively. The results of enrichment analysis showed that inflammation and immune processes significantly affected the prognosis of patients with IPF. The degree of mast and natural killer (NK) cell infiltration also increases the prognostic risk of IPF. Conclusions: We identified three hub genes as independent molecular markers to predict the prognosis of patients with IPF and constructed a prognostic model that may be helpful in promoting therapeutic gains for IPF patients.

Nivolumab monotherapy or combination therapy with ipilimumab for lung cancer: a systemic review and meta-analysis.

BACKGROUND: The high incidence and mortality of lung cancer have seriously affected human life and health. Nivolumab is a monoclonal antibody that can inhibit programmed death 1 (PD-1) and Ipilimumab is a monoclonal antibody against CTLA-4(cytotoxic T lymphocyte-associated antigen 4), both of which can prevent the immune escape of tumor cells. Our goal was to synthesize evidence from published randomized controlled trials involving the safety and efficacy of either Nivolumab alone or in combination for the treatment of unresectable lung cancer. METHODS: We searched the following electronic databases: PubMed, Embase, and Cochrane libraries, and screened the retrieved records for eligibility. We used the Stata16 software for the analyses. The results of the analysis are expressed as hazard ratios (HRs) or risk ratios (RRs) and their corresponding 95% confidence intervals (CI). RESULTS: The final analysis included seven trials involving 3817 patients. Among patients with advanced lung cancer, patients using immunotherapy had better overall survival (OS), progression-free survival (PFS), and an objective response rate (ORR) than patients receiving chemotherapy. The HR of Nivolumab monotherapy or combination therapy with OS was compared with that of chemotherapy (HR: 0.73, 95% CI 0.64-0.83; HR: 0.67, 95% CI 0.55-0.81), and the HR of PFS was (HR: 0.81, 95% CI 0.69-0.94; HR: 0.67, 95% CI 0.55-0.82). CONCLUSIONS: Immunotherapy has been shown to have more clinically meaningful survival benefits for patients with lung cancer, whether monotherapy or combination immunotherapy. CRD42020213440.

Hypoxia-induced long non-coding RNA plasmacytoma variant translocation 1 upregulation aggravates pulmonary arterial smooth muscle cell proliferation by regulating autophagy via miR-186/Srf/Ctgf and miR-26b/Ctgf signaling pathways.

BACKGROUND: The lncRNA PVT1 reportedly functions as a competing endogenous RNA (ceRNA) of miR-186 and miR-26b in different tissue types. In this study, we investigated the possible involvement of the miR-186/Srf/Ctgf and miR-26b/Ctgf signaling pathways in the pathogenesis of hypoxia-induced PAH. METHODS: Expression of PVT1, miR-186, miR-26b, and Srf and Ctgf mRNAs were evaluated by real-time polymerase chain reaction. Protein expression of SRF, CTGF, LC3B-I, LC3B-II, and Beclin-I was evaluated using western blotting. The regulatory relationship between the lncRNA, miRNAs, and target mRNAs was explored using luciferase assays. Immunohistochemistry was used to evaluate the expression of SRF and CTGF in situ. MTT assay was performed to assess the proliferation of PASMCs. RESULTS: Exposure to hypoxia markedly altered the expression of PVT1, Srf, Ctgf, miR-186, and miR-26b in a rat model. MiR-186 binding sites in the sequences of Srf mRNA and PVT1 were confirmed by luciferase assays, indicating that miR-186 may interact with both PVT1 and Srf mRNA. Additionally, miR-26b binding sites were identified in the sequences of Ctgf mRNA and PVT1, suggesting that miR-26b may interact with both PVT1 and Ctgf mRNA. In line with this, we found that overexpression of PVT1 reduced expression of miR-26b and miR-186 but activated expression of Srf, Ctgf, LC3B-II, and Beclin-I. CONCLUSIONS: Upregulation of PVT1 by exposure to hypoxia promoted the expression of CTGF, leading to deregulation of autophagy and abnormal proliferation of PASMCs. Dysregulation of the miR-186/Srf/Ctgf and miR-26b/Ctgf signaling pathways may be involved in the pathogenesis of hypoxia-induced PASMCs.

High Expression of DEPDC1B Predicts Poor Prognosis in Lung Adenocarcinoma.

Introduction: Lung adenocarcinoma (LUAD) is the most common type of lung cancer. DEP domain-containing 1 B (DEPDC1B) is involved in the development of several cancers; however, its role in LUAD is unknown. Therefore, we aimed to determine the biological function and prognostic value of DEPDC1B in LUAD. Material and Methods: We analyzed the correlation between DEPDC1B expression and the clinical features of LUAD and lung squamous cell carcinoma (LUSC). Survival was evaluated by generating Kaplan-Meier curves, which were used to analyze the relationship between DEPDC1B expression and prognosis in LUAD and LUSC. DEPDC1B expression in tumor and normal tissues from patients with LUAD and LUSC was determined using immunohistochemistry, and its clinical significance was analyzed. Finally, the correlation between the expression and biological function of DEPDC1B in LUAD was examined. Results: Our findings revealed that DEPDC1B expression was higher in tumor tissues than that in normal tissues from patients with LUAD and LUSC (P < 0.001). These results were confirmed in clinical samples from patients using immunohistochemistry. Analysis of a dataset from The Cancer Genome Atlas (TCGA) showed that high DEPDC1B expression was associated with poor prognosis only in patients with LUAD (P < 0.001). Similarly, high DEPDC1B expression was related to shorter overall survival (OS) and progression-free interval (PFI) in patients with LUAD. These associations were not observed in LUSC. Functional enrichment analysis suggested that DEPDC1B promoted tumor development in LUAD by regulating the cell cycle. Conclusion: High DEPDC1B expression predicts poor prognosis in patients with LUAD. Thus, DEPDC1B has potential as a therapeutic target for LUAD.

The cuproptosis related genes signature predicts the prognosis and correlates with the immune status of clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (CCRCC) has a high incidence and poor prognosis. Cuproptosis, an independent pattern of cell death associated with copper, plays an important role in cancer proliferation and metastasis. The role of cuproptosis-related genes (CRGs) in CCRCC is unclear. Methods: Transcriptome and clinical information for CCRCC were downloaded from The Cancer Genome Atlas (TCGA) database. After dividing the training and testing cohort, a 4-CRGs risk signature (FDX1, DLD, DLAT, CDKN2A) was identified in the training cohort using Least absolute shrinkage and selection operator (LASSO) and Cox regression analysis. The effect of the 4-CRGs risk signature on prognosis was assessed using Kaplan-Meier (KM) curves and time-dependent receiver operating characteristic (ROC) curves and verified using the testing cohort. For different risk groups, the immune statue was assessed using the CIBERSORT algorithm, the ssGSEA method and immune checkpoint expression data. Finally, a competitive endogenous RNA (ceRNA) network was constructed using miRTarbase and starBase databases to identify molecules that may have a regulatory relationship with CRCCC. Results: There were significant changes in the overall survival (OS), immune microenvironment, immune function, and checkpoint gene expression among the different risk groups. A ceRNA network consisting of one mRNA, two miRNAs, and 12 lncRNAs was constructed. Conclusion: The 4-CRGs risk signature provides a new method to predict the prognosis of patients with CCRCC and the effect of immunotherapy. We propose a new cuproptosis-associated ceRNA network that can help to further explore the molecular mechanisms of CCRCC.

Effect of Methylation Status of lncRNA-MALAT1 and MicroRNA-146a on Pulmonary Function and Expression Level of COX2 in Patients With Chronic Obstructive Pulmonary Disease.

This study aimed to investigate the role of methylation of MALAT1 and miR-146a in the pathogenesis of chronic obstructive pulmonary disease (COPD). COPD patients were grouped according to their methylation status of MALAT1 and miR-146a promoters, and we found that forced vital capacity, volume that has been exhaled at the end of the first second of forced expiration, and diffusion capacity for carbon monoxide were the highest in the MALAT1 HYPO + miR-146a HYPER group and lowest in the MALAT1 HYPER + miR-146a HYPO group, and COPD patients with hypermethylated MALAT1 showed lower expression of MALAT1 than that in the COPD patients with hypomethylated MALAT1. Meanwhile, miR-146a was the most significantly upregulated in the MALAT1 HYPER + miR-146a HYPO group and the most significantly downregulated in the MALAT1 HYPO + miR-146a HYPER group. Both prostaglandin E1 and cyclooxygenase 2 (COX2) expression were the highest in the MALAT1 HYPO + miR-146a HYPER group and the lowest in the MALAT1 HYPER + miR-146a HYPO group. In conclusion, our results established a MALAT1/miR-146a/COX2 signaling axis. The overexpression of MALAT1 could increase the expression of COX2 by inhibiting the expression of miR-146a, thus affecting the pulmonary function of COPD patients.