Genetic-based tool improves pancreatic cancer treatment decisions

Researchers in Japan have developed a predictive model that could improve treatment decisions for advanced pancreatic cancer patients. By combining tumor marker readings with patients' genetic information, their model predicts patient survival outcomes with greater accuracy and better identifies candidates who would benefit from surgery. The researchers found that specific genetic variations have a greater impact on tumor marker levels than the severity of the cancer. 

It is expected that the new model will be used as an indicator to determine if surgery is a good option for patients receiving chemotherapy or radiation treatment. The study was published in the British Journal of Surgery. 

Tumor Marker Gene Model 

A tumor marker is a substance found in the body that may indicate the presence of cancer. These substances can be proteins, genes, molecules, or other biological compounds that are produced by cancer cells or by the body in response to cancer.  

Doctors normally evaluate tumor marker levels using standardized reference ranges or by measuring percentage changes in their levels during treatment. However, traditional tumor markers used to decide on treatment options are unreliable indicators on their own because they differ significantly between patients.  

Genetic variants of specific genes affect how tumor markers are produced in an individual’s body. Some people have genetic variants that naturally result in higher or lower levels of these markers, regardless of the state of the disease. This means that two patients with identical cancer severity might show very different tumor marker readings simply because they have different genetic profiles. 

The new “Tumor Marker Gene Model” (TMGM) addresses this limitation by including genetic information when making a prognosis. The model assesses the patient's genotype—the complete set of genetic information or DNA sequences that an organism inherits from its parents—to determine what should be considered normal or elevated tumor marker levels for individual patients. 

Researchers analyzed DNA from pancreatic cancer patients and found that FUT2 and FUT3 genotypes significantly impacted patients’ survival outcomes. These genes influence what are considered normal tumor marker levels when no cancer is present. They affect an individual’s ability to synthesize tumor markers and how these markers appear in blood tests when cancer is present. 

The new model incorporates these two genotypes with tumor marker levels. Results showed more accurate survival prediction rates for patients with tumors initially classified as inoperable (before receiving chemotherapy or radiation treatment). The TMGM had approximately 15% more accuracy than the standard model. This suggests that current tumor marker evaluations are inadequate for these genetic profiles. 

Identifying candidates for surgery 

Tumors classified as inoperable are usually too risky to remove through surgery, however, treatments such as chemotherapy and radiation therapy can be used to shrink these tumors and make surgery feasible. The difficulty is determining which patients would benefit from surgery. 

The researchers found that the TMGM was particularly valuable for making these decisions. By assessing genetic information alongside tumor marker changes, doctors could more accurately identify which patients with tumors initially classified as inoperable would likely benefit from surgery after treatment.  

Importantly, the researchers found that tumor marker levels were more closely linked to a patient’s genetic makeup than to how advanced their cancer was. This suggests that genetic information is crucial for accurately interpreting what changes in tumor markers mean for individual patients. This finding is significant because doctors rely on tumor markers to assess cancer severity and treatment response. Therefore, interpreting these markers without considering genetics could lead to incorrect conclusions about a patient's condition or treatment effectiveness.  

“We found that the TMGM could more accurately identify which patients would really benefit from surgery. This could prevent some from undergoing unnecessary procedures and offer surgical opportunities to others who might have been overlooked,” Prof. Haruyoshi Tanaka from the Department of Surgery at Nagoya University Hospital and first author stated. 

The study was conducted by researchers from Nagoya University, Nagoya Medical Center, and Toyama University.