AI Reveals Pregnancy Proteins Linked to Poorer Outcomes in Female Lung Cancer Patients, Suggesting New Treatment Targets

Lung cancer can activate genes that are usually involved in fetal development, specifically pregnancy-specific glycoproteins (PSGs). While these genes can be active in both men and women with lung cancer, a team from Memorial Sloan Kettering Cancer Center (MSK) has discovered that female patients with PSG-activated tumors have significantly worse survival rates compared to their male counterparts. This finding was presented at the American Association for Cancer Research Annual Meeting. Background on PSGs Pregnancy-specific glycoproteins are produced by the placenta during pregnancy. They play a crucial role in supporting fetal development by regulating the maternal immune system, ensuring it does not attack the growing fetus. In cancer, PSG genes can be hijacked to help tumors evade the immune system and grow more aggressively. Study Findings: Sex Differences in Lung Cancer Outcomes The MSK research team, led by first author Jung Hun Oh, Ph.D., and senior author Joseph Deasy, Ph.D., utilized machine learning to analyze RNA-Seq expression datasets from two large databases: The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). The TCGA dataset included 235 male and 271 female patients, while the CPTAC dataset included 70 male and 36 female patients. Their analysis revealed that female lung cancer patients with PSG expression had poorer outcomes than males with the same condition. Specific PSG Genes and KRAS Pathway The study identified several specific PSG genes whose activation was associated with particularly poor prognoses in female patients. Additionally, the researchers noted a significant correlation between PSG expression and changes in the KRAS signaling pathway, which is a critical gene for cell growth and division and is commonly mutated in lung cancer. Notably, PSG expression did not worsen outcomes for male patients, suggesting a unique interaction in females. Validation and Impact on Survival The findings from the TCGA dataset were validated in the CPTAC dataset, where the negative impact on overall survival was even more pronounced. This validation strengthens the credibility of the results and highlights a potential therapeutic target specific to female patients. Potential Therapeutic Strategies Dr. Deasy and his team propose that targeting PSG-related pathways could offer a new approach to improving survival rates for female lung cancer patients. Since PSGs are typically inactive outside of pregnancy, they present a promising and specific drug target. Future research will focus on understanding the intricate relationship between PSG expression and KRAS pathway activation, as well as exploring the influence of pregnancy history and hormone-related genes on lung cancer outcomes. Next Steps The research team plans to expand on these findings by conducting further studies to unravel the complex interplay between PSG expression and KRAS pathway changes. They also aim to investigate how pregnancy history and hormonal factors may contribute to the observed differences in lung cancer survival rates between genders. Understanding these mechanisms could lead to more personalized and effective treatments for female patients. Industry Insights and Company Profiles Industry experts acknowledge the significance of this research, highlighting its potential to break new ground in gender-specific cancer treatments. The findings suggest that biological differences between men and women may play a critical role in cancer progression and response to therapy. Dr. Oh and Dr. Deasy's work at MSK demonstrates the power of integrating artificial intelligence with genomic data to uncover hidden patterns and advance precision medicine. Memorial Sloan Kettering Cancer Center is a world-renowned institution dedicated to the prevention, treatment, and research of cancer. Its interdisciplinary approach and cutting-edge technology, including the use of AI, have positioned MSK as a leader in developing innovative cancer therapies. This study exemplifies MSK's commitment to understanding and addressing the unique challenges faced by different patient populations, particularly in terms of sex-based disparities in cancer outcomes.