Project title: Molecular Influences of Racial Disparities in Pancreatic Neuroendocrine Tumors

Description

Dr. Bart Rose’s research project focuses on understanding the epigenetic differences driving disparate outcomes between Black and Caucasian patients with pancreatic neuroendocrine tumors (PNETs). His project involves confirming the differences in epigenetic modulators and gene expression and using that information to determine the different methylation status and gene expression in resected specimens from patients who have PNETs.

What question will you try to answer through your research?

Research has uncovered disparities in the clinical outcomes between Caucasian and minority patients with PNETs, particularly Black patients. Black patients with PNETs are more likely to present with metastatic disease, are less likely to undergo curative surgery, and have a 20% worse overall survival than white patients. However, Black patients who have their tumors resected have the same overall survival as white patients. Dr. Rose and his colleagues are working to determine which epigenetic mutation is driving early tumor metastasis in Black patients.

Why is this important?

The differences in DNA methylation between Black and Caucasian patients who have PNETs have not been investigated, despite the fact that differences have been found with respect to other cancers, such as breast, prostate, colon, and endometrial cancer. A better understanding of these driver mutations may therefore provide insight into new drugs to treat advanced PNET disease.

What will you do as part of this research project?

We will explore the epigenetic differences in PNETs through complex sequencing experiments as well as cutting-edge microscopic evaluations looking at the interaction between patients’ normal cells and the immune system.

How might your research improve the treatment of NETs?

We hope to identify new mutations that can be targeted in the future by drugs specific to neuroendocrine tumors, especially those present in Black patients with PNETs.

What is the next step?

We have already started collecting the tumor specimens from our patients and will start the sequencing analysis later this year.

Outcomes:

Pancreatic neuroendocrine tumors are uncommon cancers that form from the hormone-producing cells of the pancreas. Some of these tumors make hormones that cause severe symptoms, including dangerous blood sugar swings, severe diarrhea, heart problems, and ulcers. Unfortunately, more than half of patients are diagnosed after the cancer has already spread, which means surgery is no longer an option. Treatments like somatostatin analogs or targeted radiation may help control symptoms, but they do not offer long-term control of the disease. Our research focused on understanding why Black patients with these tumors tend to do worse than White patients. Studies show that Black patients are more likely to be diagnosed when their cancer has already spread, less likely to have surgery, and have overall worse survival. Yet, when Black patients do receive surgery, their survival matches that of White patients. We looked deeper and discovered that even among patients with smaller tumors, Black patients were more likely to already have cancer in their lymph nodes. This raises the possibility that the tumors in Black patients may be more aggressive because of differences in the biology of the cancer itself, not just differences in care.

To test this, we compared tumor samples from Black and White patients to see if the genes that control tumor behavior are different between the two groups. We used advanced methods to examine gene activity and how genes are regulated in the tumor cells. We found that 246 genes were expressed differently between the two groups. Some of the most affected biological pathways in Black patients’ tumors involved the body’s hormone systems, internal biological clock, and nervous system development. To narrow down which genes might actually make tumors more aggressive, we focused on those that were not only different between groups but also linked to the spread of cancer to the lymph nodes. We identified 15 such genes. These genes are now strong candidates for future studies that may uncover how they drive cancer progression and how they could be targeted for treatment.

This research is important because it challenges the idea that health disparities are only due to unequal access to care. While that remains a major factor, we show that there may also be biological differences in the tumors themselves. By understanding these differences, we hope to develop new tools to better predict which tumors are more aggressive, personalize treatment for patients of all backgrounds, and ultimately improve survival for everyone. This study contributes to cancer research by highlighting the importance of including racially diverse patients in genomic studies. Our work is a step toward more equitable, biologically-informed cancer care for all people living with pancreatic neuroendocrine tumors.

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