Multi-omic analysis reveals metabolic pathways that characterize right-sided colon cancer liver metastasis

Authors

Montana T. Morris, Department of Surgery/Surgical Oncology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA.Follow
Abhishek Jain, Department of Environmental Health Sciences, Yale School of Public Health, 60 College Street, New Haven, CT, 06510, USA.Follow
Boshi Sun, Department of Surgery/Surgical Oncology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA.Follow
Vadim Kurbatov, Department of Surgery/Surgical Oncology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA.Follow
Engjel Muca, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.Follow
Zhaoshi Zeng, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.Follow
Ying Jin, Department of Surgery/Surgical Oncology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA.
Jatin Roper, Department of Medicine/Gastroenterology, Duke University School of Medicine, 124 Davison Building, Durham, NC, 27710, USA.Follow
Jun Lu, Department of Genetics, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06378, USA.Follow
Philip B. Paty, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.Follow
Caroline H. Johnson, Department of Environmental Health Sciences, Yale School of Public Health, 60 College Street, New Haven, CT, 06510, USA. Electronic address: caroline.johnson@yale.edu.Follow
Sajid A. Khan, Department of Surgery/Surgical Oncology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA. Electronic address: Sajid.khan@yale.edu.Follow

Document Type

Article

Publication Title

Cancer letters

Abstract

There are well demonstrated differences in tumor cell metabolism between right sided (RCC) and left sided (LCC) colon cancer, which could underlie the robust differences observed in their clinical behavior, particularly in metastatic disease. As such, we utilized liquid chromatography-mass spectrometry to perform an untargeted metabolomics analysis comparing frozen liver metastasis (LM) biobank samples derived from patients with RCC (N = 32) and LCC (N = 58) to further elucidate the unique biology of each. We also performed an untargeted RNA-seq and subsequent network analysis on samples derived from an overlapping subset of patients (RCC: N = 10; LCC: N = 18). Our biobank redemonstrates the inferior survival of patients with RCC-derived LM (P = 0.04), a well-established finding. Our metabolomic results demonstrate increased reactive oxygen species associated metabolites and bile acids in RCC. Conversely, carnitines, indicators of fatty acid oxidation, are relatively increased in LCC. The transcriptomic analysis implicates increased MEK-ERK, PI3K-AKT and Transcription Growth Factor Beta signaling in RCC LM. Our multi-omic analysis reveals several key differences in cellular physiology which taken together may be relevant to clinical differences in tumor behavior between RCC and LCC liver metastasis.

First Page

216384

DOI

10.1016/j.canlet.2023.216384

Publication Date

10-10-2023

Recommended Citation

Morris, Montana T.; Jain, Abhishek; Sun, Boshi; Kurbatov, Vadim; Muca, Engjel; Zeng, Zhaoshi; Jin, Ying; Roper, Jatin; Lu, Jun; Paty, Philip B.; Johnson, Caroline H.; and Khan, Sajid A., "Multi-omic analysis reveals metabolic pathways that characterize right-sided colon cancer liver metastasis" (2023). Surgery. 221.
https://scholar.bridgeporthospital.org/surgery/221

Identifier

37716465 (pubmed); NIHMS1934623 (mid); PMC10620771 (pmc); 10.1016/j.canlet.2023.216384 (doi); S0304-3835(23)00335-X (pii)