Asparagine Metabolism in Tumors Is Linked to Poor Survival in Females with Colorectal Cancer: A Cohort Study

Authors

Xinyi Shen, Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT 06510, USA.Follow
Yuping Cai, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA.Follow
Lingeng Lu, Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT 06510, USA.Follow
Huang Huang, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA.Follow
Hong Yan, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA.Follow
Philip B. Paty, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.Follow
Engjel Muca, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.Follow
Nita Ahuja, Division of Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, CT 06510, USA.Follow
Yawei Zhang, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA.Follow
Caroline H. Johnson, Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA.Follow
Sajid A. Khan, Division of Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, CT 06510, USA.Follow

Document Type

Article

Publication Title

Metabolites

Abstract

The interplay between the sex-specific differences in tumor metabolome and colorectal cancer (CRC) prognosis has never been studied and represents an opportunity to improve patient outcomes. This study examines the link between tumor metabolome and prognosis by sex for CRC patients. Using untargeted metabolomics analysis, abundances of 91 metabolites were obtained from primary tumor tissues from 197 patients (N = 95 females, N = 102 males) after surgical colectomy for stage I-III CRC. Cox Proportional hazard (PH) regression models estimated the associations between tumor metabolome and 5-year overall survival (OS) and recurrence-free survival (RFS), and their interactions with sex. Eleven metabolites had significant sex differences in their associations with 5-year OS, and five metabolites for 5-year RFS. The metabolites asparagine and serine had sex interactions for both OS and RFS. Furthermore, in the asparagine synthetase (ASNS)-catalyzed asparagine synthesis pathway, asparagine was associated with substantially poorer OS (HR (95% CI): 6.39 (1.78-22.91)) and RFS (HR (95% CI): 4.36 (1.39-13.68)) for female patients only. Similar prognostic disadvantages in females were seen in lysophospholipid and polyamine synthesis. Unique metabolite profiles indicated that increased asparagine synthesis was associated with poorer prognosis for females only, providing insight into precision medicine for CRC treatment stratified by sex.

DOI

10.3390/metabo12020164

Publication Date

2-9-2022

Recommended Citation

Shen, Xinyi; Cai, Yuping; Lu, Lingeng; Huang, Huang; Yan, Hong; Paty, Philip B.; Muca, Engjel; Ahuja, Nita; Zhang, Yawei; Johnson, Caroline H.; and Khan, Sajid A., "Asparagine Metabolism in Tumors Is Linked to Poor Survival in Females with Colorectal Cancer: A Cohort Study" (2022). Surgery. 182.
https://scholar.bridgeporthospital.org/surgery/182

Identifier

35208238 (pubmed); PMC8875032 (pmc); 10.3390/metabo12020164 (doi); metabo12020164 (pii)