Translational oncology · 2025
Multi-omics characterization identifies AHCY as a prognostic biomarker driving immunometabolic reprogramming in bladder cancer.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Peng Qiao, Zhang Mengmei, Zhao Shuyu, Guo Yadong, Shan Minjue, Su Baimei, Mao Shiyu, Shi Donghui, Lin Ziyou
Аннотация
INTRODUCTION: Bladder cancer (BLCA) is a heterogeneous malignancy with poor prognosis and limited biomarkers for risk stratification and therapy guidance. Adenosylhomocysteinase (AHCY), a key enzyme in the methionine cycle, has been implicated in tumor progression and epigenetic regulation, but its clinical and biological significance in BLCA remains unclear.
METHODS: We performed an integrative pan-cancer and BLCA-focused analysis using TCGA, GTEx, and multiple independent datasets. Multi-omics data, including transcriptomic, genomic, epigenetic, immune, and drug sensitivity profiles, were systematically analyzed. Prognostic associations were evaluated by Cox and Kaplan-Meier analyses, and in vitro knockdown assays were conducted to assess AHCY function in BLCA cells.
RESULTS: AHCY was significantly upregulated across diverse cancers and correlated with poor overall, disease-specific, and progression-free survival. In BLCA, AHCY overexpression was driven by copy number amplification and promoter hypomethylation, and was associated with enhanced cell cycle progression, DNA replication, and pyrimidine metabolism, while negatively linked to apoptosis and immune activation. High AHCY expression correlated with immune infiltration but impaired effector responses, predicted poor immunotherapy outcomes, and conferred resistance to chemotherapeutics and targeted agents across PRISM, CTRP, and GDSC datasets. Functional assays confirmed that AHCY depletion suppressed proliferation, induced apoptosis, and promoted ferroptosis by downregulating SLC7A11 and upregulating ACSL4 and 4-HNE.
CONCLUSIONS: Our findings identify AHCY as a prognostic biomarker and immunometabolic regulator in BLCA, linking methionine metabolism to tumor progression, immune suppression, and drug resistance. AHCY holds promise as a therapeutic target and companion biomarker for precision oncology.
METHODS: We performed an integrative pan-cancer and BLCA-focused analysis using TCGA, GTEx, and multiple independent datasets. Multi-omics data, including transcriptomic, genomic, epigenetic, immune, and drug sensitivity profiles, were systematically analyzed. Prognostic associations were evaluated by Cox and Kaplan-Meier analyses, and in vitro knockdown assays were conducted to assess AHCY function in BLCA cells.
RESULTS: AHCY was significantly upregulated across diverse cancers and correlated with poor overall, disease-specific, and progression-free survival. In BLCA, AHCY overexpression was driven by copy number amplification and promoter hypomethylation, and was associated with enhanced cell cycle progression, DNA replication, and pyrimidine metabolism, while negatively linked to apoptosis and immune activation. High AHCY expression correlated with immune infiltration but impaired effector responses, predicted poor immunotherapy outcomes, and conferred resistance to chemotherapeutics and targeted agents across PRISM, CTRP, and GDSC datasets. Functional assays confirmed that AHCY depletion suppressed proliferation, induced apoptosis, and promoted ferroptosis by downregulating SLC7A11 and upregulating ACSL4 and 4-HNE.
CONCLUSIONS: Our findings identify AHCY as a prognostic biomarker and immunometabolic regulator in BLCA, linking methionine metabolism to tumor progression, immune suppression, and drug resistance. AHCY holds promise as a therapeutic target and companion biomarker for precision oncology.