Research presented at the American Association for Cancer Research Annual Meeting reveals that genes normally associated with pregnancy could be contributing to poorer outcomes for women with lung cancer. A team of researchers from Memorial Sloan Kettering Cancer Center (MSK) found that pregnancy-specific glycoproteins (PSGs), which help support a developing fetus, are activated in lung cancer, and their presence may worsen survival rates in female patients.
During pregnancy, the placenta produces PSGs that regulate the mother’s immune system to prevent it from rejecting the fetus. Previous MSK studies have shown that PSG genes are activated in approximately 20% of patients with cancers such as lung, breast, uterus, and colon, and those patients tend to experience worse prognoses.
Building on this research, the new study reveals key differences between male and female lung cancer patients whose cancers express PSG genes. These findings suggest that targeting these genes could improve survival rates for female lung cancer patients, according to the researchers.
Using machine learning, the MSK team, led by senior author Dr. Joseph Deasy, Chair of the Department of Medical Physics, discovered that female lung cancer patients whose cancers expressed PSG genes had significantly poorer outcomes compared to their male counterparts. Notably, when multiple specific PSG genes were activated, the prognosis for female patients was especially dire.
The study also uncovered a potential explanation for these gender differences: female patients with PSG expression often exhibited changes in the KRAS signaling pathway, which is known to play a crucial role in cell growth and division. KRAS mutations are frequently found in lung cancer, and their interaction with PSG expression appears to worsen the prognosis for women. In contrast, PSG expression did not significantly affect outcomes in male lung cancer patients.
The analysis was based on two RNA-Seq expression datasets. One dataset, which included 235 male and 271 female patients from The Cancer Genome Atlas (TCGA), was validated using another cohort of 70 male and 36 female patients from the Clinical Proteomic Tumor Analysis Consortium (CPTAC). In the latter group, the impact of PSG expression on overall survival was even more pronounced.
Building on these findings, the research team plans to seek additional grant funding to further explore the connection between PSG expression and KRAS pathway activation. They also aim to investigate how pregnancy history and hormone-related genes may influence these outcomes.
Dr. Deasy, senior author of the study, emphasized that targeting PSG-related pathways could offer a new strategy for improving survival rates in female lung cancer patients. Given that PSGs are typically not expressed outside of pregnancy, they could serve as a promising target for therapeutic intervention.
The research was supported by the National Cancer Institute (R01CA285801, P30CA008748) and the Breast Cancer Research Foundation (BCRF-17-193). Additional authors include Gabrielle Rizzuto, MD, PhD, Rena Elkin, PhD, Corey Weistuch, PhD, and Larry Norton, MD, of MSK; and Gabriela Dveksler, PhD, of the Uniformed Services University of Health Sciences. Dr. Norton has disclosed several outside consulting roles and honoraria, while Dr. Deasy is a co-founder of PAIGE.AI. For further details, please refer to the conference abstract.
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