Researchers have discovered that uterine serous carcinoma tumors in Black patients tend to express more aggressive and immunosuppressive features than tumors in White patients, according to a recent study published by Foley et al in Proceedings of the National Academy of Sciences.
Uterine serous carcinoma is a rare and aggressive type of endometrial cancer, comprising up to 10% of all primary endometrial cancer cases, according to the Foundation for Women’s Cancer. The 5-year survival rate for patients with advanced-stage tumors is around 30%. The cancer also disproportionately affects Black women, with previous research showing differences in cancer driver mutations in tumors from Black patients vs White patients.
“Our environment, socioeconomic status, and societal stressors can all impact us psychologically,” said senior author Julie Kim, PhD, the Susy Y. Hung Research Professor of Obstetrics and Gynecology at Northwestern Feinberg School of Medicine. “If the environmental insults are chronic, they can have an impact on health. We are seeing differences in these tumors in terms of the genes they express, in terms of the immune system and the immune response.”
Study Details and Findings
The scientists investigated the molecular and genomic differences in uterine serous carcinoma tumors between Black and White patients by performing single-nuclei RNA sequencing of tumor samples from four White patients and nine Black patients. “These tumors are very rare, so it’s difficult to get samples,” Dr. Kim said. “We had to rely on tumor banks established to obtain these samples.”
From these samples, the investigators discovered that tumors from Black patients demonstrated increased expression of genes associated with tumor aggressiveness—notably PAX8, which is commonly increased in other endometrial cancers and in ovarian cancer—compared with White patients. Patients who had tumors with increased PAX8 expression also had worse overall survival compared with patients who had low PAX8 expression, according to the authors.
Furthermore, they discovered that PAX8 directly influenced the activity of macrophages within the uterine serous carcinoma tumor microenvironment to suppress antitumor immune responses, and that this was more prevalent in tumors from Black patients. “This is the first time PAX8 has been investigated for its involvement with immune signaling,” said first study author K. Grace Foley, a PhD candidate in Dr. Kim’s lab. “Hopefully, this work can contribute to our understanding of endometrial cancer and improve survival for these patients.”
The findings may inform new strategies to improve disparities in patient outcomes, according to Dr. Kim. They underscore the clinical relevance of increased PAX8 in uterine serous carcinoma, especially in Black patients, which may serve as a potential therapeutic target.
The next steps include duplicating the findings in a larger patient cohort and identifying current drugs that may help tumors with increased PAX8 expression better respond to the immune system. “It'll be important to test what we found in a larger cohort to make sure this is indeed something that is fundamentally different between Black and White women,” Dr. Kim said. “We want to gather more data, so we can be confident in potentially testing compounds in preclinical studies before going toward clinical trials.”
Disclosure: For full disclosures of the study authors, visit pnas.org.
