ABSTRACT
Background: Globally, non-small-cell lung cancer (NSCLC) is one of the most prevalent tumors. Various studies have investigated its etiology, but the molecular mechanism of NSCLC has not been elucidated. Methods: The GSE19804, GSE118370, GSE19188, GSE27262, and GSE33532 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database for the identification of genes involved in NSCLC development as well as progression. Then, the identified differentially expressed genes (DEGs) were subjected to functional enrichment analyses. The protein-protein interaction (PPI) network was built after which module analysis was conducted via the Search Tool for Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape. There were 562 DEGs: 98 downregulated genes and 464 upregulated. These DEGs were established to be enriched in p53 signaling pathway, transendothelial leukocyte migration, cell adhesion molecules, contractions of vascular smooth muscles, coagulation and complement cascades, and axon guidance. Assessment of tumor immunity was performed to determine the roles of hub genes. Results: There were 562 dysregulated genes, while 12 genes were hub genes. NUF2 was established to be a candidate immunotherapeutic target with potential clinical implications. The 12 hub genes were highly enriched in the p53 signaling pathway, the cell cycle, progesterone-associated oocyte maturation, cellular senescence, and oocyte meiosis. Survival analysis showed that NUF2 is associated with NSCLC occurrence, invasion, and recurrence. Conclusion: The NUF2 gene discovered in this study helps us clarify the pathomechanisms of NSCLC occurrence as well as progression and provides a potential diagnostic and therapeutic target for NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Cell Cycle Proteins , Lung Neoplasms , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell Cycle Proteins/genetics , Computational Biology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Prognosis , Tumor Suppressor Protein p53/geneticsABSTRACT
Mild cognitive impairment (MCI) is inconclusively associated with regional gray matter (GM) abnormalities in Parkinson's disease (PD). We aimed to quantitatively evaluate whole-brain voxel-based morphometry (VBM) studies that have investigated brain GM changes in PD patients with MCI (PD-MCI). Seed-based d Mapping, a well-validated coordinate-based meta-analytic approach, was utilized. We included 20 VBM studies that reported 22 datasets containing 504 patients with PD-MCI and 554 PD patients without MCI (PD-NCI). The most reliable finding identified in this meta-analysis was that patients with PD-MCI exhibited greater GM atrophy in the left anterior insula than those with PD-NCI. Our findings further suggest that several moderators (age, gender, educational level, disease stage, severity of motor disability, and the severity of cognitive impairments) in PD-MCI individuals, as well as scanner field-strength, may drive heterogeneous GM changes across studies. GM abnormalities in the anterior insula, an important cognitive hub involved in switching between neural networks, contribute to understanding the neural substrates of MCI in PD, which may serve as a biomarker of PD-MCI.
