There have been demonstrated differences in tumor cell metabolism between right-sided and left-sided colorectal tumors, which could explain the differences observed in their clinical behavior, especially in metastatic disease. Now, new research has found that patients with right-sided colorectal tumors that spread to the liver had worse survival rates than those with left-sided tumors that had also metastasized to the liver. The findings, published by Morris et al in Cancer Letters, provide insight into the unique biology of right- and left-sided tumors, which may impact treatment options and patient outcomes.
Study Methodology
The researchers used liquid chromatography–mass spectrometry and RNA sequencing to perform an untargeted metabolomic and genetic characteristic analysis comparing frozen liver metastasis biobank samples derived from patients with right-sided (n = 32) and left-sided colon cancer (n = 58) to understand the unique biology of each tumor.
Results
The metabolomic results from the study demonstrated increased reactive oxygen species–associated metabolites and bile acids in the right-side colon cancer samples. Conversely, carnitines, indicators of fatty acid oxidation, were relatively increased in the samples of left-sided colon cancer. The transcriptomic analysis implicated increased MEK-ERK, P13K-AKT, and transcription growth factor beta (TGF-b) pathway signaling in right-sided colon cancer liver metastasis.
“Our multiomic analysis reveals several key differences in cellular physiology, which, taken together, may be relevant to clinical differences in tumor behavior between right-sided colon cancer and left-sided colon cancer liver metastasis,” concluded the study authors.
Clinical Significance
“These findings show that metastatic tumors to the liver originating from different locations in the colon have distinct behaviors,” said senior study author Sajid A. Khan, MD, FACS, FSSO, Associate Professor of Surgery and Section Chief, Hepato-Pancreato-Biliary and Mixed Tumors at Yale School of Medicine, in a statement. “This knowledge will help us tailor treatment strategies and improve outcomes for patients with liver metastases, no matter what side of the colon they originate from.”
Dr. Khan, of Yale School of Medicine, and Caroline H. Johnson, PhD, of the Yale School of Public Health, are co–corresponding authors for this paper.
Disclosure: Funding for this study was provided by the National Institutes of Health, American Cancer Society, Lampman Surgical Oncology, Yale University, and Yale University School of Medicine. For full disclosures of the study authors, visit sciencedirect.com.
