Researchers identified distinct metabolic signatures that differentiate cancer patients with and without gallstones, potentially supporting noninvasive screening.


Researchers have identified distinct chemical signatures in blood that could help detect gallbladder cancer earlier, offering a potential pathway toward noninvasive screening for one of the deadliest gastrointestinal cancers.

The study, led by scientists at Tezpur University in Assam, India, working with researchers at the University of Illinois Urbana-Champaign, found specific metabolic patterns that distinguish gallbladder cancer cases from noncancerous conditions in both patients with and without gallstones. The findings were published in the Journal of Proteome Research.

Using advanced metabolomics techniques, the team analyzed blood samples from three groups: gallbladder cancer patients without gallstones, cancer patients with gallstones, and individuals with gallstones but no cancer. The researchers detected hundreds of altered metabolites—180 in gallstone-free cancer cases and 225 in gallstone-associated cases—and identified distinct markers with high diagnostic accuracy for each condition.

“Our findings show that changes in certain blood metabolites can clearly distinguish gallbladder cancer cases with and without gallstones. This raises the possibility of developing simple blood-based tests that could support earlier diagnosis,” says assistant professor Pankaj Barah, PhD, at Tezpur University, who led the study, in a release.

Computational Analysis Reveals Disease Mechanisms

Many of the identified metabolites were linked to bile acids and amino acid derivatives known to play roles in tumor development and progression. The computational metabolomics analysis, led by assistant professor Amit Rai in the Department of Crop Sciences at the University of Illinois, helped differentiate overlapping metabolic signals and clarify how cancer-related changes differ depending on patients’ gallstone status.

“Once the raw data are generated, the real challenge is making biological sense of it,” says Rai, in a release. “Properly annotating metabolites and analyzing their patterns is what allows us to move from signals in the data to meaningful insight about disease mechanisms.”

The research addresses a significant clinical challenge, as gallbladder cancer often isn’t detected until advanced stages, contributing to its poor prognosis. The disease affects approximately 12,000 people annually in the US, with roughly 2,000 deaths. Globally, incidence varies widely, with much higher rates in regions such as northern India’s Assam state, where the disease is among the most common cancers.

Clinical Applications Still Need Validation

The study’s clinical collaborator emphasized the potential practical applications of the findings. “Identifying blood-based metabolic markers provides a practical pathway toward earlier diagnosis and more informed clinical decision-making,” says study co-author Subhash Khanna, gastrointestinal surgeon at Swagat Super Speciality and Surgical Hospital in India, in a release.

However, the researchers emphasize that larger, multicenter studies are needed before the findings can be used clinically. The work lays important groundwork for noninvasive screening tools, particularly in high-risk regions, and highlights the growing role of international collaborations in advancing cancer research.

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