Lung Cancer Outcomes Linked to PSG Genes in Women

Researchers at Memorial Sloan Kettering Cancer Center (MSK) have uncovered a surprising link between pregnancy-specific glycoproteins (PSGs) and poorer lung cancer outcomes in women. These proteins, typically expressed by the placenta during pregnancy to protect the fetus, may be co-opted by cancer cells to evade the immune system.

While PSG gene activation was found in cancers of both men and women, female patients had significantly worse outcomes when these genes were expressed, according to findings presented at the American Association for Cancer Research (AACR) Annual Meeting.

How PSG Genes Influence Female Lung Cancer Survival

During pregnancy, PSGs help prevent the mother’s immune system from attacking the fetus. But this same immune-modulating effect may help cancer cells go undetected. The MSK team, led by Jung Hun Oh, PhD, and senior author Joseph Deasy, PhD, used machine learning to analyze the impact of PSG gene expression across large patient datasets.

Their results: Women whose tumors activated multiple PSG genes faced markedly worse survival rates. Interestingly, this effect was not observed in male patients.

The KRAS Connection: A Double Threat for Women

One key insight from the study was that women with PSG gene expression often showed changes in the KRAS signaling pathway—a genetic mutation commonly associated with aggressive lung cancers. This dual mechanism may help explain why PSG activation has such a strong negative impact on female outcomes.

The researchers examined data from The Cancer Genome Atlas (TCGA) and validated their findings using the Clinical Proteomic Tumor Analysis Consortium (CPTAC), covering over 600 patients. In both datasets, the combination of PSG expression and KRAS mutations was particularly lethal in women.

Implications and Next Steps

The team plans to explore whether a patient’s pregnancy history or hormone-related gene expression might influence PSG activation in tumors. Since PSGs are rarely active outside of pregnancy, they present a novel drug target with minimal off-target risks.

“Targeting PSG-related pathways could offer a powerful new strategy to improve outcomes for female lung cancer patients,” said Dr. Deasy. “It may also have broader applications in other cancers where PSGs are expressed.”

This discovery marks an important step toward gender-specific oncology research, emphasizing the need to tailor treatments based on biological differences that influence disease progression.

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