Spanish researchers identify two new biomarkers to detect anal cancer

People with HIV, especially men who have sex with men, are at increased risk of developing anal cancer.. In these patients, early detection of precancerous lesions is essential to prevent the tumor from developing. However, the techniques that are commonly used for this purpose can be greatly improved..

An international team, led by Spanish researchers, has identified two new biomarkers that could significantly improve this detection of precursor lesions of cancer (called high-grade squamous intraepithelial lesions) and, therefore, prevent the development of tumors..

Specifically, these researchers have discovered that in the anal microbiome there are two metabolites produced by bacteria that directly correlate with the aforementioned intraepithelial lesions..

As they were able to verify, the production of succinyl-coA and cobalamin is increased in the microbiome of patients with precancerous lesions.. Therefore, these metabolites may serve as useful biomarkers in clinical practice..

“Our goal is to create a diagnostic kit that allows self-sampling to measure these markers. This would mean a great saving of resources and would increase the accessibility of the diagnosis.. The ultimate goal is to improve our ability to diagnose and, therefore, treat high-grade anal dysplasia more efficiently and effectively”, explains Sergio Serrano, a researcher at the Ramón y Cajal Health Research Institute (IRYCIS), member of the Infectious Diseases service of the Ramón y Cajal University Hospital in Madrid and first signatory of the paper..

Researchers from the CIBER of Infectious Diseases, the CSIC, Hospital La Paz and the Jiménez Díaz Foundation, as well as the Universities of Hohenheim (Germany), Oslo (Norway), Bangor (United Kingdom) and Milan (Italy) have also participated in the research.

To carry out the research, the scientists have studied 213 patients, who were already undergoing follow-up with anoscopies and anal biopsies as they presented an increased risk of anal cancer, a type of cancer that is linked to papillomavirus infection..

“Our previous investigations led us to believe that we could identify a specific group of bacteria that would indicate the presence of lesions,” Serrano said via email.. This was not the case and the team came to think that it would have to end the investigation without significant results.. “However, by looking at the proteins expressed by the bacteria we discovered something fascinating.. We found a powerful statistical signal in certain proteins. In addition, these proteins were linked to two metabolic pathways previously described in bacteria that adapt to cause infections and in tumor cells that invade tissues.. In other words, there was a strong biological basis for our findings.. These proteins guided us to study two metabolites derived from these metabolic pathways: cobalamin or vitamin B12, which only bacteria can produce; and succinyl CoA, a key compound in the reactions that generate energy in cells,” says Serrano, who remembers that moment as a true “eureka” moment..

The research indicates that the combination of biomarkers is superior in diagnostic capacity to conventional anal cytology, since it improves sensitivity, specificity, and predictive values..

In addition to trying to develop a diagnostic kit, the researchers want to replicate the results in other populations, study whether these biochemical pathways represent possible treatment targets, and analyze the levels of these metabolites in other cancers originating from epithelia..

“Because of the parallels with that of the cervix, this will be the first one that we investigate,” says Serrano..

Regarding the mechanisms involved in the relationship between metabolites and precancerous lesions, the researcher clarifies that “due to the design of the study that we have already carried out, we cannot establish the causes that lead to the induction of these biochemical pathways. But given the functions of the proteins associated with the presence of precancerous lesions, we believe that they are involved in the development of these lesions.”.