Impact of BCL-2 rs2279115 and rs3943258 variants on protein expression and clinical outcome of urothelial bladder carcinoma.

چکیده اصلی

BACKGROUND: 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.

ترجمه فارسی چکیده

کارسینومای اوروتلیال مثانه (UBC) شایع‌ترین سرطان داخلی مثانه است. اهمیت این مطالعه بررسی ارتباط جهش‌های rs2279115 (G > T) و rs3943258 (T > C) و ساختار هپلوتیپ آن‌ها با بیان پروتئین BCL-2 در بیماران مبتلا به UBC است. یافته‌ها نشان می‌دهد که جهش rs2279115 با بیان مثبت BCL-2 مرتبط است. به طور خاص، ژنوتیپ TT در مدل ژنوتیپی (p = 0.035) و ژنوتیپ GT در مدل فراتر از غالبیت (p = 0.045) به وضعیت پروتئین مرتبط بوده‌اند. علاوه بر این، هپلوتیپ CT به طور مستقل با تومورهای درجه بالا مرتبط بوده است. وجود هپلوتیپ CT (هم در حالت هموژنوتی و هم هتروژنوتی) اثر ریسک ایجاد می‌کند (p = 0.020). این یافته‌ها نشان می‌دهند که جهش‌ها و بیان BCL-2 می‌توانند بینش‌های مفیدی در مورد ویژگی‌های مولکولی UBC ارائه دهند، اما نیاز به تأیید آینده دارد.

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