Robust Validation and Comprehensive Analysis of a Novel Signature Derived from Crucial Metabolic Pathways of Pancreatic Ductal Adenocarcinoma

Cancers

Chenyu Sun¹  Wenchao Gu²  Yoshito Tsushima²  Takahito Nakajima³  Shaocong Mo⁴  Yulin Wang⁵  Huaxiang Xu⁶  Wei Zhang⁷  Reika Kawabata-Iwakawa⁸  Zongcheng Yang⁹ 

[1] AMITA Health St. Joseph Hospital, Chicago, IL 60657, USA;Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan;Department of Diagnostic and Interventional Radiology, University of Tsukuba, Ibaraki 305-8577, Japan;Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200437, China;Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200437, China;Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200437, China;Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK;Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research, Maebashi 371-8511, Japan;Division of Life Sciences and Medicine, Center of Stomatology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei 230026, China;

关键词: pancreatic ductal adenocarcinoma;    metabolic pathways;    prognosis;    recurrence;    drug sensitivity;   

DOI  :  10.3390/cancers14071825

来源: DOAJ

【 摘 要 】

Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with a dismal prognosis. PDAC have extensively reprogrammed metabolic characteristics influenced by interactions with normal cells, the effects of the tumor microenvironment and oncogene-mediated cell-autonomous pathways. In this study, we found that among all cancer hallmarks, metabolism played an important role in PDAC. Subsequently, a 16-gene prognostic signature was established with genes derived from crucial metabolic pathways, including glycolysis, bile acid metabolism, cholesterol homeostasis and xenobiotic metabolism (gbcx). The signature was used to distinguish overall survival in multiple cohorts from public datasets as well as a validation cohort followed up by us at Shanghai Cancer Center. Notably, the gbcx-related risk score (gbcxMRS) also accurately predicted poor PDAC subtypes, such as pure-basal-like and squamous types. At the same time, it also predicted PDAC recurrence. The gbcxMRS was also associated with immune cells, especially CD8 T cells, Treg cells. Furthermore, a high gbcxMRS may indicate high drug sensitivity to irinotecan and docetaxel and CTLA4 inhibitor immunotherapy. Taken together, these results indicate a robust and reproducible metabolic-related signature based on analysis of the overall pathogenesis of pancreatic cancer, which may have excellent prognostic and therapeutic implications for PDAC.

【 授权许可】

Unknown