Scientists at Washington State University and Johns Hopkins Medical School have discovered a fast, noninvasive method that could lead to the early diagnosis of colorectal cancer. Using ultrasensitive, high-speed technology, the researchers identified a suite of molecules in the feces of mice that signifies the presence of precancerous polyps. This “metabolic fingerprint” matches changes in both mouse and human colon tumor tissues and suggests a potential new diagnostic tool for early detection of colorectal cancer in a clinical setting.
Herbert Hill, WSU Regents professor, and graduate student Michael Williams conducted the study in collaboration with Raymond Reeves, WSU School of Molecular Biosciences, and Linda Resar, Johns Hopkins University School of Medicine. The findings were reported this month in the Journal of Proteome Research.
Hill and Williams discovered the molecular fingerprint for colon cancer using a technology called ion mobility-mass spectrometry. Ion mobility-mass spectrometry is found in sensor devices worldwide that sniff out illicit drugs, chemical warfare agents and explosives in airports. Hill has been an innovator in the field for nearly 40 years. In this case, ion mobility-mass spectrometry was coupled with ultraperformance liquid chromatography.
The researchers first identified metabolic products from normal colon tissue in both humans and mice. Ion mobility-mass spectrometry can measure hundreds of metabolites simultaneously, such as enzymes, fats, glucose and amino acids. The scientists then compared this normal profile to that found in cancerous colon tissues from humans and research mice with polyps in their colons that mimic those in humans.
In both cases, the scientists found that colon cancer caused significant changes in fat metabolism, especially for lipids and fatty acids. These abnormalities created a molecular fingerprint that was similar in humans and mice, said Hill.
Next, Hill and Williams examined droppings from transgenic and control mice to see if the molecular fingerprint could be found in feces as well. Indeed ion mobility-mass spectrometry detected many of the same metabolic abnormalities seen in the previous study and could clearly distinguish between healthy mice and those with colorectal cancer.
“The feces was not exactly the same as the tissue samples, but it had a lot of similarities to the tissue,” said Hill. “We found the lipids and fatty acids were changing — and there were also changes in the amino acids.” Specifically, an important class of fats called lysophospholipids changed dramatically, said Williams. “These types of lipids are known to be important in the development of cancer and are particularly tied to colorectal cancer.”
Their next step, if funded, is to evaluate human stool samples to see if the molecular fingerprint is present with colorectal cancer in people.
Citation: The Fecal Metabolome in Hmga1 Transgenic Mice with Polyposis: Evidence for Potential Screen for Early Detection of Precursor Lesions in Colorectal Cancer.
Authors: Williams, Michael David, et., al.
Journal: Journal of Proteome Research
Adapted from press release by Washington State University