Pregnancy-associated proteins worsen survival in women with lung cancer

Lung cancer can use genes that normally help the fetus develop and avoid the mother’s immune system. And while these pregnancy-specific glycoproteins (PSGs) can be activated in both male and female cancers, female patients had a worse prognosis. This was reported by the research team at Memorial Sloan Kettering Cancer Center (MSK).

According to an analysis presented at this year’s annual meeting of the American Association for Cancer Research, targeting these genes may improve the survival rate of female patients with lung cancer.

Genes that protect the fetus … and cancer?

During pregnancy, the placenta produces a number of proteins, PSGs, that help carry the pregnancy to term, including regulating the mother’s immune system so it doesn’t perceive the fetus as a potential threat, says study first author Jung Hun Oh, PhD, an associate researcher in MSK’s Department of Medical Physics.

A previous MSK study found that PSG genes are activated in about 20% of patients with lung, breast, uterine and colorectal cancers, and that these patients typically have worse outcomes.

The new study builds on these findings by identifying significant differences in outcomes between male and female patients who have these PSG genes activated in their lung tumors.

Using artificial intelligence to understand sex differences in lung cancer outcomes

Using artificial intelligence, the team, led by senior author Joseph Dicey, PhD, chair of the Department of Medical Physics, showed that female patients whose cancer tumors have activated PSG genes suffer significantly more than male patients. Moreover, the analysis showed that when several specific PSG genes were activated, the prognosis was particularly poor.

The researchers also found a clue that may help explain these differences: women with PSG-expressing lung cancer also often had alterations in the KRAS signaling pathway. Mutations in the KRAS gene, which is important for cell growth and division, are common in lung cancer. However, PSG expression in male lung cancer patients did not worsen their prognosis.

The analysis was performed using two different RNA-Seq expression datasets. The data included 235 men and 271 women from The Cancer Genome Atlas (TCGA), and were validated on 70 men and 36 women from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), where the effect on overall survival was even stronger.

Next steps

The research team plans to build on the findings and further investigate the relationship between PSG expression and KRAS pathway activation, as well as explore the role that pregnancy history and hormone-related genes play.

“Targeting PSG-related pathways represents a new strategy to potentially improve outcomes for patients with lung cancer and possibly other cancers in which PSGs are activated,” Dr. Dicey said. Because PSGs are not normally expressed outside of pregnancy, they may be a promising drug target.

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Published: 10.05.2025

Updated: 10.05.2025

Medical author, Medical editor:

Stepan Yuk

Medical expert:

PhD. Olexandr Voznyak