Genetic-Based Tool Predicts Survival Outcomes of Pancreatic Cancer Patients

A tumor marker is a substance found in the body that may signal the presence of cancer. These substances, which can include proteins, genes, molecules, or other biological compounds, are either produced by cancer cells or by the body in response to cancer. Doctors typically assess tumor marker levels using standardized reference ranges or by measuring percentage changes in marker levels during treatment. However, traditional tumor markers, when used alone to guide treatment decisions, are often unreliable because they can vary significantly between patients. Genetic variants of specific genes influence how tumor markers are produced in an individual's body. Some people have genetic variations that naturally lead to higher or lower levels of these markers, regardless of the presence of disease. As a result, two patients with the same cancer severity might show very different tumor marker levels simply due to differences in their genetic profiles.

Researchers at Nagoya University (Nagoya, Japan) have now developed a predictive model that could enhance treatment decisions for patients with advanced pancreatic cancer. By combining tumor marker readings with genetic information, the model can more accurately predict survival outcomes and better identify patients who would benefit from surgery. The researchers discovered that certain genetic variations had a greater impact on tumor marker levels than the severity of the cancer itself. This new model is expected to be used as a tool to determine whether surgery is a viable option for patients undergoing chemotherapy or radiation. The “Tumor Marker Gene Model” (TMGM) incorporates genetic information into the prognosis. It evaluates the patient’s genotype—the full set of genetic information inherited from their parents—to establish what constitutes normal or elevated tumor marker levels for that specific individual.

The research team analyzed the DNA of pancreatic cancer patients and identified that the FUT2 and FUT3 genotypes significantly influenced the patients’ survival outcomes. These genes help determine what is considered a normal level of tumor markers in the absence of cancer. They also affect an individual’s ability to produce tumor markers and how these markers appear in blood tests when cancer is present. The TMGM combines these genotypes with tumor marker levels, and the results showed a more accurate prediction of survival rates for patients whose tumors were initially classified as inoperable before undergoing chemotherapy or radiation. The TMGM demonstrated about 15% greater accuracy than the standard model, suggesting that current tumor marker evaluations are insufficient for patients with these specific genetic profiles.

Typically, tumors classified as inoperable are considered too risky to remove through surgery, but treatments like chemotherapy and radiation can reduce the size of these tumors, making surgery a possibility. The challenge lies in determining which patients will benefit from surgery. The researchers found that the TMGM was especially useful in making these decisions. By combining genetic information with changes in tumor markers, doctors could more accurately identify which patients with tumors initially classified as inoperable would likely benefit from surgery following treatment. Importantly, the researchers found that tumor marker levels were more closely associated with a patient’s genetic makeup than the stage of their cancer. This suggests that genetic data is crucial for accurately interpreting what changes in tumor markers indicate 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 genetic factors could lead to incorrect conclusions about a patient’s condition or the effectiveness of their treatment.

“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,” said Prof. Haruyoshi Tanaka from the Department of Surgery at Nagoya University Hospital and first author of the study published in the British Journal of Surgery.

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