SC Connecticut News

A recent study from the Yale School of Public Health (YSPH) provides new insights into colorectal cancer (CRC), challenging the traditional classification of tumors as right-sided or left-sided. The location of a tumor significantly affects prognosis and survival, with left-sided tumors being more common and easier to detect than right-sided ones, which have poorer prognoses.

The research team, led by Abhishek Jain, Caroline Helen Johnson, and Dr. Sajid A. Khan, MD, has created the first comprehensive CRC metabolome map. This map reveals distinct metabolic profiles across various subsites of the colorectum, potentially leading to more precise diagnostics and treatments tailored to individual tumors' metabolic environments.

"Our findings indicate a continuum in changes to metabolite concentrations, which underscores the need for a more nuanced classification of CRC beyond the simplistic right-versus-left-side dichotomy," said Johnson, an associate professor at YSPH and a senior author of the study.

Published in Molecular Cancer journal, the study used liquid chromatography-mass spectrometry to analyze metabolic profiles in 372 patient-matched tumor and normal mucosa tissues across seven colorectum subsites: cecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectosigmoid colon, and rectum. The researchers identified significant alterations in metabolites between these regions.

One key finding is that metabolite abundances change gradually from cecum to rectum rather than abruptly at anatomical boundaries. "This continuum suggests that metabolic processes do not change abruptly but rather evolve along the length of the colon," explained Jain.

The developed metabolome map serves as a resource for understanding CRC biology further. It highlights subsite-specific differences in cancer metabolism affecting diagnostics and treatment strategies. For instance, levels of certain metabolites were linked to patient survival rates and varied distinctly across subsites.

To promote broader use of their data, researchers designed a publicly accessible CRC metabolome database. "In creating this database," Johnson said, "we aim to provide a powerful tool for researchers and clinicians."

These findings have significant implications for future CRC research and treatment by moving beyond conventional classifications toward enhanced biomarker identification accuracy and therapeutic specificity. “Understanding the metabolic heterogeneity of CRC could transform how we approach cancer care,” said Khan.

The study also opens avenues for further research into how these metabolic differences influence tumor development and patient survival. "Our findings lay a robust foundation for future investigations," Jain noted.

Researchers from Memorial Sloan Kettering Cancer Center in New York; Technology Centre of Catalonia in Spain; and Strathclyde Institute of Pharmacy & Biomedical Sciences contributed to this study.