RESUMEN
Background: The combination of deep learning methods and oncogenomics can provide an effective diagnostic method for malignant tumors; thus, we attempted to construct a reliable artificial neural network model as a novel diagnostic tool for Bladder cancer (BLCA). Methods: Three expression profiling datasets (GSE61615, GSE65635, and GSE100926) were downloaded from the Gene Expression Omnibus (GEO) database. GSE61615 and GSE65635 were taken as the train group, while GSE100926 was set as the test group. Differentially expressed genes (DEGs) were filtered out based on the logFC and FDR values. We also performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to explore the biological functions of the DEGs. Consequently, we utilized a random forest algorithm to identify feature genes and further constructed a neural network model. The test group was given the same procedures to validate the reliability of the model. We also explored immune cells' infiltration degree and correlation coefficients through the CiberSort algorithm and corrplot R package. The qRT-PCR assay was implemented to examine the expression level of the feature genes in vitro. Results: A total of 265 DEGs were filtered out and significantly enriched in muscle system processes, collagen-containing and focal adhesion signaling pathways. Based on the random forest algorithm, we selected 14 feature genes to construct the neural network model. The area under the curve (AUC) of the training group was 0.950 (95% CI: 0.850-1.000), and the AUC of the test group was 0.667 (95% CI: 0.333-1.000). Besides, we observed significant differences in the content of immune infiltrating cells and the expression levels of the feature genes. Conclusion: After repeated verification, our neural network model had clinical feasibility to identify bladder cancer patients and provided a potential target to improve the management of BLCA.
RESUMEN
This study was to determine the impact of maternal exposure to di-n-butyl phthalate (DBP) on renal development and fibrosis in adult offspring. Pregnant rats received DBP at a dose of 850 mg/kg BW/day by oral perfusion during gestational days 14-18. In DBP exposed newborn offspring, gross observation and histopathological examination revealed the dysplasia of kidney. The expression of genes related to renal development was also changed. In DBP exposed adult offspring, histopathological examination and Masson's trichrome staining revealed the pathological changes of renal fibrosis. Furthermore, higher expression levels of transforming growth factor- ß (TGF-ß) and alpha-smooth muscle actin (α-SMA) were also detected. In vitro studies reveal that DBP promoted the activation of NRK49F cells and G2/M arrest in NRK52E cells at a sublethal dose. The effect of DBP on these cell lines was linked to the generation of oxidative stress. In addition, DBP induced oxidative stress in both renal fibroblasts and tubular epithelial cells, whereas vitamin C ameliorated the changes caused by DBP. In conclusion, our results showed that prenatal exposure to DBP may generate oxidative stress in both renal fibroblasts and tubular epithelial cells, leading to kidney dysplasia and renal fibrosis.
