Background The most important health benefit of selenium (Se) is in the prevention and control of cancer. Glutathione peroxidases (GPXs) and thioredoxin reductases (TXNRDs) are selenoenzymes that are thought to play a role in oxidative stress. The differential expression of genes of the TXNRD and GPX families is closely related to carcinogenesis and the occurrence of cancer. This study comprehensively analyzed the expression profiles of seven genes in the TXNRD and GPX families, in terms of their correlations with patient survival and immune-cell subtypes, tumor microenvironment, and drug sensitivity. Results The expression profiles of genes in the TXNRD and GPX families differ between different types of cancer, and also between and within individual cancer cases. The expression levels of the seven analyzed genes are related to the overall survival of patients. The TXNRD1 and TXNRD3 genes are mainly related to poor prognoses, while other genes are related to good or poor prognoses depending on the type of cancer. All of the genes were found to be correlated to varying degrees with immune-cell subtypes, level of mechanistic cell infiltration, and tumor cell stemness. The TXNRD1, GPX1, and GPX2 genes may exert dual effects in tumor mutagenesis and development, while the TXNRD1, GPX1, GPX2, and GPX3 genes were found to be related to drug sensitivity or the formation of drug resistance. Conclusions The results will greatly help in identifying the association between genes and tumorigenesis, especially in the immune response, tumor microenvironment, and drug resistance, and very important when attempting to identify new therapeutic targets.
Background: The aim of this study was to establish a comprehensive nomogram for the cancer-specific survival (CSS) of patients with upper-tract urothelial carcinoma (UTUC) and compare it with the traditional American Joint Committee on Cancer (AJCC) staging system in order to determine its reliability. Methods: This study analyzed 9505 patients with UTUC in the Surveillance, Epidemiology, and End Results (SEER) database. R software was used to randomly divided the patients in a 7-to-3 ratio to form a training cohort (n = 6653) and a validation cohort (n = 2852). Multivariable Cox regression was used to identify predictive variables. The new survival model was compared with the AJCC prognosis model using the concordance index (C-index), the area under the time-dependent receiver operating characteristics curve (AUC), the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA). Results: We have established a nomogram for determining the 3-, 5-, and 8-year CSS probabilities of UTUC patients. The nomogram indicates that the AJCC stage has the greatest influence on CSS in UTUC, followed by the age at diagnosis, surgery status, tumor size, radiotherapy status, histological grade, marital status, chemotherapy status, race, and finally sex. The C-index was higher for the nomogram than the AJCC staging system in both the training cohort (0.785 versus 0.747) and the validation cohort (0.779 versus 0.739). Calibration plotting demonstrated that the model has good calibration ability. The AUC, NRI, IDI, and DCA of the nomogram showed that it performs better than the AJCC staging system alone.
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