RESUMO
Background: The abnormal expression of Alpha-1,3-mannosyltransferase (ALG3) has been implicated in tumor promotion. However, the clinical significance of ALG3 in Lung Adenocarcinoma (LUAD) remains poorly understood. Therefore, we aimed to assess the prognostic value of ALG3 and its association with immune infiltrates in LUAD. Methods: The transcriptional expression profiles of ALG3 were obtained from the Cancer Genome Atlas (TCGA), comparing lung adenocarcinoma tissue with normal tissues. To determine the prognostic significance of AGL3, Kaplan-Meier plotter, and Cox regression analysis were employed. Logistic regression was utilized to analyze the association between ALG3 expression and clinical characteristics. Additionally, a receiver operating characteristic (ROC) curve and a nomogram were constructed. To explore the underlying mechanisms, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene set enrichment analysis (GSEA) was conducted. The relationship between AGL3A mRNA expression and immune infiltrates was investigated using the tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB). Furthermore, an in vitro experiment was performed to assess the impact of ALG3 mRNA on lung cancer stemness abilities and examine key signaling pathway proteins. Results: Our results revealed the ALG3 mRNA and protein expression in patients with LUAD was much higher than that in adjacent normal tissues. High expression of ALG3 was significantly associated with N stage (N0, HR = 1.98, P = 0.002), pathological stage (stage I, HR = 2.09, P = 0.003), and the number of pack years (<40, HR = 2.58, P = 0.001). Kaplan-Meier survival analysis showed that high expression of ALG3 was associated with poor overall survival (P < 0.001), disease-free survival (P < 0.001), and progression-free interval (P = 0.007). Through multivariate analysis, it was determined that elevated ALG3 expression independently impacted overall survival (HR = 1.325, P = 0.04). The Tumor Immune Estimation Resource discovered a link between ALG3 expression and tumor-infiltrating immune cells in LUAD. Additionally, ROC analysis proved that ALG3 is a reliable diagnostic marker for LUAD (AUC:0.923). Functional pathways analysis identified that ALG3 is negatively correlated with FAT4. We performed qRT-PCR to assess that knockdown ALG3 expression significantly upregulated FAT4 expression. Spheroid assay and flow cytometry analysis results showed that downregulated of ALG3 inhibited H1975 cell line stemness. Western blot analysis revealed that decreased ALG3 inhibited the YAP/TAZ signal pathway. Conclusion: High expression of ALG3 is strongly associated with poor prognosis and immune infiltrates in LUAD.
RESUMO
BACKGROUND: The minichromosome maintenance (MCM) protein complex is important for DNA replication. Moreover, the expression of specific MCM complex components has been associated with the survival of hepatocellular carcinoma (HCC) patients. However, the expression and functional roles of minichromosome maintenance complex component 4 (MCM4) in HCC development and progression have not yet been explored. We analyzed the expression and clinical significance of MCM4, including its association with liver cancer patient survival. METHODS: Oncomine, UALCAN, and HCCDB (a database of HCC expression atlas) were used to characterize the expression of MCM4 in tumor and normal tissues. The expression of MCM4 at the protein level was confirmed based on immunohistochemistry (IHC) data obtained from the Human Protein Atlas (HPA) database. The level of MCM4 was measured in tumor and adjacent normal tissues by RT-qPCR, western blot and IHC staining. The copy number alterations (CNAs) and mutations in MCM4 were analyzed by cBioPortal, whereas the co-expression genes of MCM4 in HCC were obtained from Oncomine, and used for gene ontology and pathway analysis via the NetworkAnalyst 3.0 tool, to explore the predictive signaling pathway in HCC. RESULTS: The levels of MCM4 messenger (m)RNA and protein were found to be significantly higher in liver cancer tissues than in normal liver tissues. Kaplan-Meier analysis showed that the upregulation of MCM4 was significantly negatively correlated with the survival of HCC patients. CONCLUSIONS: Our data suggest that MCM4 may be used as a potential prognostic marker and therapeutic target for HCC.
RESUMO
Difluoroisoxazolacetophenone (DFIO) is developed as a new difluoroalkylation reagent that can be easily prepared from inexpensive starting materials. In situ remote C-C bond cleavage of DFIO affords γ,γ-difluoroisoxazole nitronate that undergoes base-catalyzed vinylogous nitroaldol additions to isatins, benzothiophene-2,3-dione, unsaturated-α-ketoesters, and cyclic 1,2-diketones. This organocatalytic debenzoate vinylogous nitroaldol reaction provides a new and mild approach for the preparation of various difluoroisoxazole-substituted 3-hydroxy-2-oxindoles.
