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代谢组学鉴定诱导性膀胱癌的致癌作用。

Metabolomic credentialing of murine carcinogen-induced urothelial cancer.

机构信息

Department of Cancer Biology, Medical Center Boulevard, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.

Department of Urology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.

出版信息

Sci Rep. 2021 Nov 11;11(1):22085. doi: 10.1038/s41598-021-99746-3.

DOI:10.1038/s41598-021-99746-3
PMID:34764423
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8585868/
Abstract

Bladder cancer (BCa) is the most common malignancy of the urinary system with increasing incidence, mortality, and limited treatment options. Therefore, it is imperative to validate preclinical models that faithfully represent BCa cellular, molecular, and metabolic heterogeneity to develop new therapeutics. We performed metabolomic profiling of premalignant and non-muscle invasive bladder cancer (NMIBC) that ensued in the chemical carcinogenesis N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) mouse model. We identified the enriched metabolic signatures that associate with premalignant and NMIBC. We found that enrichment of lipid metabolism is the forerunner of carcinogen-induced premalignant and NMIBC lesions. Cross-species analysis revealed the prognostic value of the enzymes associated with carcinogen-induced enriched metabolic in human disease. To date, this is the first study describing the global metabolomic profiles associated with early premalignant and NMIBC and provide evidence that these metabolomic signatures can be used for prognostication of human disease.

摘要

膀胱癌（BCa）是泌尿系统最常见的恶性肿瘤，发病率、死亡率不断上升，治疗选择有限。因此，验证能够真实反映 BCa 细胞、分子和代谢异质性的临床前模型，开发新的治疗方法迫在眉睫。我们对化学致癌 N-丁基-N-（4-羟丁基）亚硝胺（BBN）小鼠模型中发生的癌前病变和非肌肉浸润性膀胱癌（NMIBC）进行了代谢组学分析。我们确定了与癌前病变和 NMIBC 相关的丰富代谢特征。我们发现，脂质代谢的富集是致癌物诱导的癌前病变和 NMIBC 病变的前兆。种间分析揭示了与致癌物诱导的富集代谢相关的酶在人类疾病中的预后价值。迄今为止，这是第一项描述与早期癌前病变和 NMIBC 相关的全局代谢组学特征的研究，并提供了证据表明这些代谢组学特征可用于预测人类疾病。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b2/8585868/4d26a741f38d/41598_2021_99746_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b2/8585868/1c377343d3e0/41598_2021_99746_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b2/8585868/11b343b87ba2/41598_2021_99746_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b2/8585868/c8d591479b6c/41598_2021_99746_Fig10_HTML.jpg

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