Uterine cancer tumors are more aggressive in black patients than in white patients

Northwestern Medicine researchers have found that uterine serous carcinoma (USC) tumors in black patients express more aggressive and immunosuppressive features than tumors in white patients, according to a new study published Aug. 12 in the Journal of the American Journal of Clinical Oncology. Proceedings of the National Academy of Sciences.

Endometrial cancer is a rare and aggressive type of endometrial cancer, accounting for up to 10% of all primary endometrial cancer cases, according to the Foundation for Women’s Cancer. The five-year survival rate for patients with advanced cancer is about 30%.

Cancer also disproportionately affects black women, with previous research showing differences in cancer driver mutations in tumors from black patients compared to white patients.

“Our environment, our socioeconomic status and societal stressors can all impact us psychologically,” said lead author Julie Kim, the Susy Y. Hung Research Professor of Obstetrics and Gynecology at Northwestern Feinberg School of Medicine.

“If environmental stresses are chronic, they can impact health. We see differences in these tumors in terms of the genes they express, in terms of the immune system and the immune response.”

Along with senior author Kim, the lead author is Grace Foley, a student in Driskill’s graduate program in life sciences. Mazhar Adli, the Thomas J. Watkins Memorial Professor of Tumor Genomics and assistant professor of obstetrics and gynecology, was a co-author of the study.

Kim and Adli are also members of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University.

Scientists investigated molecular and genomic differences in USC tumors between black and white patients by performing single-nuclear RNA sequencing of USC tumor samples from four white patients and nine black patients.

“These tumors are very rare, so it’s difficult to get samples,” Kim said. “We had to rely on tumor banks that were set up to get these samples.”

From these samples, the researchers found that tumors from black patients had increased expression of genes associated with tumor aggressiveness, including PAX8, which is typically increased in other endometrial cancers and in ovarian cancer, compared to white patients.

According to the authors, patients with tumors with increased PAX8 expression also had worse overall survival compared to patients with low PAX8 expression.

Additionally, they found that PAX8 directly influences the activity of macrophages – specialized white blood cells that kill cancer cells and stimulate other immune cells – in the USC tumor microenvironment to suppress anti-tumor immune responses, and that this was more common in tumors from black patients.

“This is the first time that PAX8’s role in immune signaling has been studied,” Foley said. “We hope this work will contribute to our understanding of endometrial cancer and improve survival for these patients.”

Kim said these findings could inform new strategies to improve disparities in patient outcomes. They underscore the clinical relevance of increased PAX8 in USC, particularly in black patients, which could serve as a potential therapeutic target, Kim said.

Next steps in the research include duplicating their findings in a larger patient cohort and identifying current drugs that can help tumors with increased PAX8 expression better respond to the immune system.

“It will be important to test what we found in a larger cohort to make sure this is indeed a fundamental difference between black and white women,” Kim said. “We want to collect more data so we can confidently test the compounds in preclinical studies before moving to clinical trials.”