Liver samples can predict the spread of pancreatic cancer

Microscopic changes in the liver can be used to predict whether and where pancreatic cancer will spread in the body. This discovery has the potential to contribute to new ways to predict the course of the disease and prevent pancreatic cancer from spreading to other organs. This study, led by Weill Cornell Medical College in the USA, was conducted in collaboration with researchers at Linköping University, among others, and was published in the journal Natural medicine.

Cancer cells have several characteristics that distinguish them from healthy cells in the same tissue. One of these characteristics, which many tumors develop, is the ability to spread daughter tumors to other organs. This process is called metastasis. But there are many questions about how this happens, and what causes certain tumors of the same type to spread and others not.

The current study was also published in the journal Natural medicine, focuses on pancreatic cancer metastasis after surgery. Pancreatic cancer spreads mainly to the liver. There is a great need to be able to perform risk assessment at an early stage to find patients most at risk of developing liver metastases.

Once the tumor spreads to the liver, most pancreatic cancer patients unfortunately die from the cancer. One of the goals of this study was to try to capture what happens in the early stages when cancer spreads to the liver, says Konstantinos Zamperinis, an associate professor at Linköping University and a surgeon at Linköping University Hospital.

For more than a hundred years, scientists have observed that metastasis does not occur randomly. There are patterns in which a particular type of cancer spreads to organs most often. According to one theory, the interaction between the tumor and the recipient organ is essential for new tumors to survive there. This theory is called the “seed and soil” hypothesis. Much research has focused on the properties of the “seed,” the original tumor, that promote metastasis. On the other hand, the researchers in the current study wanted to investigate what role the “soil,” the organ to which the cancer spreads, might play in this process.

Previous research by the Weill Cornell Medical College research team, led by David Leiden, has shown that the original tumor can send signals to other organs and initiate changes that allow the new tumors to grow there. In other words: According to this theory, metastasis begins long before cancer cells reach other organs. But those studies had never been done in humans, primarily in mice. The question was whether it worked the same way in humans.

In collaboration with Memorial Sloan Kettering Cancer Center, researchers collected tissue samples from the livers of 49 patients who underwent surgery for pancreatic cancer. At the time of the operation, there were no signs of the cancer spreading. They also took samples from the livers of 19 patients who did not have cancer but underwent similar procedures for other reasons. The researchers then followed the study participants' performance over the next three years.

Significant differences were found in the livers of patients with metastatic pancreatic cancer compared to the control group without cancer. These changes in the livers of cancer patients were related, among other things, to the immune system and increased inflammation. However, the group of patients whose cancer had not spread had livers that looked relatively similar to those of the control group. These findings support the hypothesis that the original tumor sends signals that lead to changes in other organs, creating a so-called pre-metastatic niche where cancer cells have an easier time growing into daughter tumors.

Among patients who later developed daughter tumors in the liver, the cancer appeared to spread there at different rates. In their analysis, the researchers divided the cancer patients into groups: early spread to the liver, within six months after surgery, and late spread to the liver, after more than six months. There was also a group of patients whose cancer spread to the lungs or other organs, and a group whose cancer never spread at all. The researchers found small but significant differences in metabolism, gene expression and immune cells in livers that spread quickly compared with livers that took longer to spread or were absent altogether.

Based on the results of the various analyses, the research team developed a machine learning model to predict whether pancreatic cancer is likely to spread, based on characteristics present in a tissue sample taken from the liver at the time of diagnosis.

“This study changes the clinical context for pre-metastatic liver biopsies not only in pancreatic cancer but also in other forms of cancer, such as colorectal cancer and gastric cancer, in the hope of knowing the likelihood and course of the disease,” says David Leiden, MD, professor of pediatric cardiology and professor of pediatrics and of cell and developmental biology at Weill Cornell Medical College, New York, USA.

Such predictions can help doctors tailor cancer treatment to a patient's risk of recurrence.

“The most interesting thing is that there are differences in the liver depending on the condition of the patients. We see signs of different changes that seem to be important for the spread of cancer, which will be very interesting to follow up in larger studies,” says Linda Bogmar, an assistant lecturer at Linköping University and a researcher at Weill Cornell Medical College in the USA.

The researchers now plan to conduct a larger study of pancreatic cancer and several types of gastrointestinal cancer to see if their findings can be confirmed and investigate the cellular mechanisms.

The research was funded with support from, among others, the National Cancer Institute, the National Institutes of Health, the Cancer Fund, the Swedish Research Council, and the Swedish Society for Medical Research, SSMF.

purpose: A multiparameter atlas of pre-metastatic liver for predicting metastatic outcomes in early-stage pancreatic cancerLinda Bogmar, Konstantinos P. Zamparinis, Jonathan M. Hernandez, et al. Nature Medicine, published online June 28, 2024, doi: 10.1038/s41591-024-03075-7

For more information please contact:
Linda Bojmar, Assistant University Lecturer, [email protected], 070-0896577 (For Linda's mobile number, contact the LiU Press Service via [email protected], 013 28 13 95 or 013-28 28 00 )
Constantinos Zambirinis, Lecturer, [email protected]
David Leyden, Professor, [email protected]

High-resolution press images of the researchers can be downloaded here Leo Media Bank.

Press release sent by:
Karen Soderlund Leffler
Media communication, Linköping University
013-28 13 95/ 073-417 01 59 / 013-28 28 00 (Click on phone)
[email protected]

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