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Background: Bladder cancer (BLCA) is a prevalent malignancy affecting the urinary system and is associated with significant morbidity and mortality worldwide. Dysregulation of tumor metabolic pathways is closely linked to the initiation and proliferation of BLCA. Tumor cells exhibit distinct metabolic activities compared to normal cells, and the purine metabolism pathway, responsible for providing essential components for DNA and RNA synthesis, is believed to play a crucial role. However, the precise involvement of Purine Metabolism Genes (PMGs) in the defense mechanism against BLCA remains elusive. Methods: The integration of BLCA samples from the TCGA and GEO datasets facilitated the quantitative evaluation of PMGs, offering potential insights into their predictive capabilities. Leveraging the wealth of information encompassing mRNAsi, gene mutations, CNV, TMB, and clinical features within these datasets further enriched the analysis, augmenting its robustness and reliability. Through the utilization of Lasso regression, a prediction model was developed, enabling accurate prognostic assessments within the context of BLCA. Additionally, co-expression analysis shed light on the complex relationship between gene expression patterns and PMGs, unraveling their functional relevance and potential implications in BLCA. Results: PMGs exhibited increased expression levels in the high-risk cohort of BLCA patients, even in the absence of other clinical indicators, suggesting their potential as prognostic markers. GSEA revealed enrichment of immunological and tumor-related pathways specifically in the high-risk group. Furthermore, notable differences were observed in immune function and m6a gene expression between the low- and high-risk groups. Several genes, including CLDN6, CES1, SOST, SPRR2A, MYBPH, CGB5, and KRT1, were found to potentially participate in the oncogenic processes underlying BLCA. Additionally, CRTAC1 was identified as potential tumor suppressor genes. Significant discrepancies in immunological function and m6a gene expression were observed between the two risk groups, further highlighting the distinct molecular characteristics associated with different prognostic outcomes. Notably, strong correlations were observed among the prognostic model, CNVs, SNPs, and drug sensitivity profiles. Conclusion: PMGs have been implicated in the etiology and progression of bladder cancer (BLCA). Prognostic models corresponding to this malignancy aid in the accurate prediction of patient outcomes. Notably, exploring the potential therapeutic targets within the tumor microenvironment (TME) such as PMGs and immune cell infiltration holds promise for effective BLCA management, albeit necessitating further research. Moreover, the identification of a gene signature associated with purine Metabolism presents a credible and alternative approach for predicting BLCA, signifying a burgeoning avenue for targeted therapeutic investigations in the field of BLCA.
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Plasma homocysteine (Hcy) has been identified as a potential risk factor for cerebral small vessel disease. Cerebral small vessel disease (CSVD) leads to cognitive impairment, depression, and other symptoms and is a common disease in middle-aged and elderly people. To investigate the relationship between 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and CSVD in elderly patients, plasma levels of homocysteine (Hcy) and MTHFR genotyping were assessed. MRI and MRA were performed at the same time to analyze the relationship between different genotypes and cerebrovascular lesions. We showed that Hcy plasma levels in the TT group were significantly higher than those in the CC and CT groups. Moreover, we observed that the severity of white matter lesions was associated with women and positively correlated with age, previous coronary heart disease, luminal infarction, and MTHFR polymorphism. The multivariate logistic regression analysis showed that age, TT genotype, and lacunar infarction were independent risk factors for white matter hyperintensity (WMH). Importantly, we showed that there was a significant correlation between Hcy plasma levels and MTHFR gene polymorphism, with the TT genotype constituting an independent risk factor for WMH. Therefore, we recommended early detection of MTHFR gene polymorphisms with concomitant early intervention concerning risk factors to delay the occurrence of cognitive impairment in CSVD elderly patients.
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BACKGROUND: The apolipoprotein E (APOE) ε4 allele is considered as a risk factor for Alzheimer's disease (AD). However, the association of APOE allele with MRI evidence of intracranial lesions has not been well understood. METHODS: Quantitative real-time PCR was performed to detect the APOE genotype; MRI was examined for intracranial lesions. Their association was evaluated in a cohort of 226 AD patients and 2607 healthy individuals in southern China. RESULTS: The frequencies of ε2, ε3, and ε4 alleles were 8.0%, 82.9%, and 9.1% in the whole study population. The frequency of APOE-ε4 allele was significantly higher in the AD subjects than that in the control group (14.4% vs 8.6%, P < 0.001). We found that brain atrophy occurred at a rate of 12.3% in ε4 allele group vs 8.5% in non-ε4 genotype group, with a significance of P = 0.008. Severe brain atrophy occurred at a rate of 1.0% in ε4 allele group vs 0.2% in non-ε4 genotype group (P = 0.011). The individuals carrying APOE ε4/ε4 had an odds ratio (OR) of 7.64 (P < 0.01) for developing AD, while the APOE ε3/ε4 gene carriers had an OR of 1.47 (P = 0.031) and the OR in APOE ε2/ε3 carriers is 0.81 (P = 0.372). Interestingly, we found that the risk of ε4/ε4 allele carrier developing AD was significantly higher in male (P < 0.001) than female (P = 0.478). CONCLUSION: Compared to ε2 and ε3 alleles, the presence of APOE-ε4 allele might increase the risk for AD in a dose-dependent manner in southern China. Moreover, the presence of APOE-ε4 allele results in a higher incidence of brain atrophy.
