The extracellular matrix (ECM) is a complex and dynamic network of cross-linked proteins and a fundamental building block in multicellular organisms. Our study investigates the impact of genes related to the ECM receptor interaction pathway on immune-targeted therapy and lung adenocarcinoma (LUAD) prognosis. This study obtained LUAD chip data (GSE68465, GSE31210, and GSE116959) from NCBI GEO. Moreover, the gene data associated with the ECM receptor interaction pathway was downloaded from the Molecular Signature Database. Differentially expressed genes were identified using GEO2R, followed by analyzing their correlation with immune cell infiltration. Univariate Cox regression analysis screened out ECM-related genes significantly related to the survival prognosis of LUAD patients. Additionally, Lasso regression and multivariate Cox regression analysis helped construct a prognostic model. Patients were stratified by risk score and survival analyses. The prognostic models were evaluated using receiver operating characteristic curves, and risk scores and prognosis associations were analyzed using univariate and multivariate Cox regression analyses. A core gene was selected for gene set enrichment analysis and CIBERSORT analysis to determine its function and tumor-infiltrating immune cell proportion, respectively. The results revealed that the most abundant pathways among differentially expressed genes in LUAD primarily involved the cell cycle, ECM receptor interaction, protein digestion and absorption, p53 signaling pathway, complement and coagulation cascade, and tyrosine metabolism. Two ECM-associated subtypes were identified by consensus clustering. Besides, an ECM-related prognostic model was validated to predict LUAD survival, and it was associated with the tumor immune microenvironment. Additional cross-analysis screened laminin subunit beta 1 (LAMB1) for further research. The survival time of LUAD patients with elevated LAMB1 expression was longer than those with low LAMB1 expression. Gene set enrichment analysis and CIBERSORT analyses revealed that LAMB1 expression correlated with tumor immune microenvironment. In conclusion, a prognostic model of LUAD patients depending on the ECM receptor interaction pathway was constructed. Screening out LAMB1 can become a prognostic risk factor for LUAD patients or a potential target during LUAD treatment.
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http://dx.doi.org/10.1097/MD.0000000000039854 | DOI Listing |
Alzheimers Dement
December 2024
Baylor College of Medicine, Houston, TX, USA.
Background: Alzheimer's disease (AD) has a complex etiology where insults in multiple pathways conspire to disrupt neuronal function, yet molecular changes underlying AD remain poorly understood. Previously, we performed mass-spectrometry on post-mortem human brain tissue to identify >40 protein co-expression modules correlated to AD pathological and clinical traits. Module 42 has the strongest correlation to AD pathology and consists of 32 proteins including SMOC1, a predicted driver of network behavior and potential biomarker for AD.
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December 2024
Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Background: The Apoliproprotein E (APOE) e4 allele is the most significant genetic risk factor for late-onset Alzheimer disease (AD). However, the risk associated with the APOE e4 allele differs across populations with individuals of African ancestry having a reduced risk than individuals of European (EU) ancestry. Further, single-nuclei RNAseq analysis in autopsy samples from AD APOEε4 homozygotes with EU Local Ancestry (LA) had a significantly increased APOEε4 expression compared to those with African LA, particularly in astrocytes.
View Article and Find Full Text PDFSci Rep
January 2025
Departments of Ophthalmology, Sapporo Medical University School of Medicine, S-1 W-16, Chuo-Ku, Sapporo, 060-8543, Japan.
To elucidate the role of IGF1R inhibition in the pathogenesis of Graves' orbitopathy (GO), the effects of linsitinib (Lins) on a recombinant human TSHR antibody (M22) and IGF1 to activate TSHR and IGF1R of human orbital fibroblasts (HOFs) obtained from patients without GO (HOFs) and patients with GO (GHOFs) were studied using in vitro three-dimensional (3D) spheroid models in addition to their 2D planar cell culture. For this purpose, we evaluated 1) cellular metabolic functions by using a seahorse bioanalyzer (2D), 2) physical properties including size and stiffness of 3D spheroids, and mRNA expression of several extracellular matrix (ECM) proteins, their modulators (CCL2 LOX, CTGF, MMPs), ACTA2 and inflammatory cytokines (IL1β, IL6). Administration of IGF1 and M22 induced increases of cellular metabolic functions with the effect on HOFs being much more potent than the effect on GHOFs, suggesting that IGF1R and TSHR of GHOFs may already be stimulated.
View Article and Find Full Text PDFExpert Rev Respir Med
January 2025
School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI, USA.
Introduction: In genetically predisposed individuals, exposure to aeroallergens and infections from RNA viruses shape epithelial barrier function, leading to Allergic Asthma (AA). Here, activated pattern recognition receptors (PRRs) in lower airway sentinel cells signal epithelial injury-repair pathways leading to cell-state changes [epithelial mesenchymal plasticity (EMP)], barrier disruption and sensitization.
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Int J Med Sci
January 2025
Department of Urology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518033, China.
Evidence increasingly indicates that HPV infection plays a pivotal role in the initiation and progression of bladder cancer (BC). Yet, determining the predictive value of HPV-associated genes in BC remains challenging. We identified differentially expressed HPV-associated genes of BC patients from the TCGA and GEO databases.
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