Research Paper Volume 13, Issue 8 pp 11907—11918
GEO data mining and TCGA analysis reveal altered branched chain amino acid metabolism in pancreatic cancer patients
- 1 Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 2 The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 3 Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 4 Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 5 Department of Immunology, School of Medicine, Yangtze University, Jingzhou, China
- 6 Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Received: November 10, 2020 Accepted: March 14, 2021 Published: April 21, 2021
https://doi.org/10.18632/aging.202892How to Cite
Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.