GEO data mining and TCGA analysis reveal altered branched chain amino acid metabolism in pancreatic cancer patients.
GEO data mining and TCGA analysis reveal altered branched chain amino acid metabolism in pancreatic cancer patients.
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DOI：
10.18632/aging.202892
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发表时间：
2021-04-21
期刊：
影响因子：
--
通讯作者：
Fan H
中科院分区：
文献类型：
--
作者：
Li JY;Sun F;Yang CL;Zhou HF;Gao M;Zhang Q;Chen H;Zhou P;Xiao J;Fan H
胰腺导管腺癌（PDAC）是一种高度侵袭性的消化系统肿瘤，其5年生存率低于1%。PDAC发展的发病机制尚未完全了解。遗传倾向、慢性胰腺炎和糖尿病病史会增加PDAC的风险，而环境和饮食因素，包括吸烟、酗酒、高脂肪/蛋白质摄入以及空气污染会加剧PDAC的进展。支链氨基酸由亮氨酸、异亮氨酸和缬氨酸组成，是从食物中获得的必需氨基酸，在致癌作用中起着多方面的作用。最近的研究表明，支链氨基酸代谢影响PDAC的发展，但结果是有争议的。为了探索BCAA代谢在PDAC中的可能参与，我们利用GEO和TCGA数据库发现BCAA吸收与PDAC的发展密切相关，而BCAA分解代谢在PDAC组织中下调。此外，NOTCH和MYC差异参与肿瘤和肌肉中BCAA代谢，并且脂质合成的增强与BCAA催化剂无关。总之，我们强调支链氨基酸的吸收作为PDAC治疗的一个有前途的目标。
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor of the digestive system which has a less than 1% 5-year survival rate. The pathogenesis of PDAC development is incompletely understood. Genetic predisposition, disease history of chronic pancreatitis and diabetes elevate the risk of PDAC while environmental and dietary factors including smoking, alcohol abuse, high fat/protein intake as well as air pollution exacerbate PDAC progression. BCAAs, consisting of leucine, isoleucine and valine are essential amino acids that are obtained from food and play versatile roles in carcinogenesis. Recent studies have demonstrated that BCAA metabolism affects PDAC development but the results are controversial. To explore the possible engagement of BCAA metabolism in PDAC, we took advantage of the GEO and TCGA database and discovered that BCAA uptake is closely related to PDAC development while BCAA catabolism is down-regulated in PDAC tissue. Besides, NOTCH and MYC are differentially involved in BCAA metabolism in tumor and muscle, and enhanced lipid synthesis is independent of BCAA catabolism. Altogether, we highlight BCAA uptake as a promising target for PDAC treatment.
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影响因子：
5.6
作者：
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