Urothelial bladder carcinoma (UBC) is the ninth most common malignancy worldwide and ranks thirteenth in cancer-related mortality. A significant challenge in managing non-muscle-invasive UBC (NMIBC) is the high recurrence rate, compounded by a paucity of robust prognostic biomarkers. Given that evasion of apoptosis is a hallmark of carcinogenesis, the apoptosis regulator BCL-2 oncogene plays a critical role by negatively regulating the intrinsic apoptotic pathway, often leading to protein overexpression and malignant cell immortalization. Methods and Results: This study evaluated the BCL-2 allelic variants rs2279115 (G > T) and rs3943258 (T > C), including their haplotype structures, in association with BCL-2 immunohistochemical expression in UBC patients. Genetic and immunostaining data were analyzed alongside prognostic factors, environmental exposure, and clinical history. Furthermore, we sought to exhibit BCL-2 immunohistochemical staining patterns via immunofluorescence in selected samples. Our findings revealed that the rs2279115 variant is significantly associated with BCL-2 positive expression. Specifically, the TT genotype in the genotypic model (p = 0.035) and the GT genotype in the overdominant model (p = 0.045) were linked to protein status. Additionally, the CT haplotype was independently associated with high-grade tumors. Conclusions: The presence of the CT haplotype — in either homozygosity or heterozygosity — exerted a risk effect of high-grade (p = 0.020). In conclusion, these findings suggest that BCL-2 variants, haplotype structures, and immunohistochemical expression may offer relevant insights into the molecular characteristics of urothelial bladder cancer. Further prospective validation is needed to determine whether BCL-2 profiling can serve as a useful complementary tool for risk assessment in clinical practice.
Julia Ayumi Ikeda Kawasaki, Ariane Pereira de Souza, João Pedro Rocha Pontes et al.· Molecular Biology Reports· 0 citations
COVID‐19 severity and survival are influenced by the host immune response to SARS‐CoV‐2. Programmed cell death 1 (PD‐1), a key immune checkpoint, regulates T‐cell activation and antiviral immune balance. Since genetic variability can modulate these responses, we investigated whether the PDCD1 polymorphisms rs11568821 C > T, rs2227982 G > A, rs2227981 G > A and rs10204525 C > T are associated with COVID‐19 severity and mortality in a Brazilian cohort. A total of 366 COVID‐19 patients (165 mild, 72 moderate, and 129 severe cases) were genotyped for the four PDCD1 SNPs, and their haplotype structures were estimated. Significant differences were observed in the allele frequencies of rs11568821, and in genotypes and allele frequencies of the exonic rs2227982, among mild, moderate, and severe cases. Multinomial logistic regression identified associations between rs2227982 (dominant and overdominant models) and moderate COVID‐19, and between the rs2227981 AA genotype (genotypic and recessive models) and severe COVID‐19. The rs10204525 polymorphism (CT genotype under genotypic dominant and overdominant models) also presented an association with severe COVID‐19. However, none of these associations remained independent. Haplotype analysis identified five major haplotypes with significantly different frequencies among the groups (p = 0.02); however, no association was found between the haplotypes and disease severity or outcome. This is the first study to evaluate SNP rs2227982 in COVID‐19 patients, and the first to evaluate the four aforementioned SNPs in a Brazilian population. Overall, our findings suggest that these polymorphisms, although involved in COVID‐19 immunopathogenesis, are not suitable biomarkers for predicting COVID‐19 severity or clinical outcomes.
S. L. Moretto, Pedro Luis Candido de Souza Cassela, G. L. Trigo et al.· Journal of Medical Virology· 0 citations
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