Single-Cell Sequencing Analysis and Multiple Machine Learning Methods Identified G0S2 and HPSE as Novel Biomarkers for Abdominal Aortic Aneurysm.

Identifying biomarkers for abdominal aortic aneurysms (AAA) is key to understanding their pathogenesis, developing novel targeted therapeutics, and possibly improving patients outcomes and risk of rupture. Here, we identified AAA biomarkers from public databases using single-cell RNA-sequencing, weighted co-expression network (WGCNA), and differential expression analyses. Additionally, we used the multiple machine learning methods to identify biomarkers that differentiated large AAA from small AAA. Biomarkers were validated using GEO datasets. CIBERSORT was used to assess immune cell infiltration into AAA tissues and investigate the relationship between biomarkers and infiltrating immune cells. Therefore, 288 differentially expressed genes (DEGs) were screened for AAA and normal samples. The identified DEGs were mostly related to inflammatory responses, lipids, and atherosclerosis. For the large and small AAA samples, 17 DEGs, mostly related to necroptosis, were screened. As biomarkers for AAA, G0/G1 switch 2 (G0S2) (Area under the curve [AUC] = 0.861, 0.875, and 0.911, in GSE57691, GSE47472, and GSE7284, respectively) and for large AAA, heparinase (HPSE) (AUC = 0.669 and 0.754, in GSE57691 and GSE98278, respectively) were identified and further verified by qRT-PCR. Immune cell infiltration analysis revealed that the AAA process may be mediated by T follicular helper (Tfh) cells and the large AAA process may also be mediated by Tfh cells, M1, and M2 macrophages. Additionally, G0S2 expression was associated with neutrophils, activated and resting mast cells, M0 and M1 macrophages, regulatory T cells (Tregs), resting dendritic cells, and resting CD4 memory T cells. Moreover, HPSE expression was associated with M0 and M1 macrophages, activated and resting mast cells, Tregs, and resting CD4 memory T cells. Additional, G0S2 may be an effective diagnostic biomarker for AAA, whereas HPSE may be used to confer risk of rupture in large AAAs. Immune cells play a role in the onset and progression of AAA, which may improve its diagnosis and treatment.

SNX20 Expression Correlates with Immune Cell Infiltration and Can Predict Prognosis in Lung Adenocarcinoma.

BACKGROUND: Sorting nexin-20 (SNX20) is a member of the sorting nexin family of proteins. It plays a crucial role in the regulation of innate immunity. However, the prognostic risk, potential mechanisms, immunotherapy, and other functions of SNX20 in lung adenocarcinoma (LUAD) remain unclear. METHODS: We analyzed and validated the expression and prognostic role of SNX20 in LUAD through a combination of The Cancer Genome Atlas, Gene Expression Omnibus, Oncomine, TIMER, and Human Protein Atlas databases. Further, we analyzed the correlation between SNX20 expression and clinical characteristics of LUAD, and the prognostic value of SNX20 in LUAD was evaluated. Using fitted SNX20 expression and other clinical parameters, a predictive model with predictive performance for the overall survival of patients with LUAD was constructed. The potential biological function of SNX20 in LUAD was explored using gene set enrichment analysis. In addition, we analyzed the correlation between SNX20 expression and the immune microenvironment and survival. RESULTS: SNX20 was downregulated in most cancer types, was associated with poor prognosis in LUAD and could be an independent prognostic factor for patients with LUAD. The predictive model developed by us had good predictive power for determining the overall survival of patients with LUAD. Biofunctional analysis revealed that genes co-expressed with SNX20 mainly promoted the immune process and inhibited the cell proliferation process in LUAD. We observed that high expression of SNX20 was accompanied by a better immune microenvironment and survival in patients with LUAD. Furthermore, the LUAD immune response was elevated with an increase in SNX20 expression. Finally, we found that SNX20 expression was significantly associated with various tumor-infiltrating immune cells, and it was widely involved in regulating various immune molecules in LUAD and affecting immune infiltration in the tumor microenvironment. CONCLUSION: Our results suggested that SNX20 is a potential immune-related biomarker and therapeutic target associated with the prognosis of patients with LUAD. This provided a new strategy for the development of immunotherapeutic and prognostic markers in LUAD.