Matthew Shinkle , 2025-05-07 18:00:00
Key takeaways:
- Female patients whose lung cancer had pregnancy-specific glycoprotein expression had worse survival outcomes.
- A treatment strategy that targets these proteins could improve outcomes.
Female patients with lung adenocarcinoma that has pregnancy-specific glycoprotein expression appear to have worse survival outcomes, according to research presented at American Association for Cancer Research Annual Meeting.
Pregnancy-specific glycoproteins (PSGs) regulate immune tolerance during pregnancy and prevent fetal rejection, according to study background.
Previous research from Memorial Sloan Kettering Cancer Center has shown that PSG genes are activated in approximately 20% of patients with lung cancer, breast cancer, uterine cancer and colon cancer. These patients typically have worse outcomes.
“Given the pregnancy-related function of PSGs and our previous finding linking PSG expression to cancer survival, we hypothesized a sex-dependent behavior of PSGs in cancer patients,” Jung Hun Oh, PhD, associate attending computer scientist in the department of medical physics at Memorial Sloan Kettering Cancer Center, told Healio. “Our pan-cancer analysis, particularly in lung cancer, supported this hypothesis.”
Oh and colleagues analyzed sex-specific effects of PSGs as prognostic markers using data from 506 patients (women, n = 271; men, n = 235) in The Cancer Genome Atlas. They also included 106 patients (women, n = 36; men, n = 70) from Clinical Proteomic Tumor Analysis Consortium to validate the data.
The researchers incorporated PSG expression levels into machine learning models to predict survival outcomes.
Results showed that women with lung adenocarcinoma who expressed PSG genes had worse survival outcomes than female patients without this expression. This finding was not observed among male patients.
Analysis also showed that a combination of PSG3, PSG7 and PSG8 expression appeared indicative of an even poorer prognosis for female patients.
“Our study revealed a sex-specific negative impact of PSG expression on survival in female lung cancer patients, suggesting PSGs as potential drug targets for approximately 30% of these patients with PSG expression,” Oh said.
Additional analysis showed that female patients with lung cancer who exhibit PSG expression also exhibited changes in the KRAS signaling pathway, which researchers say could suggest a potential mechanism underlying the observed sex-specific effects.
Including KRAS activity in the machine learning model improved performance in predicting survival outcomes for female patients, but not for male patients.
“Based on the potential of PSGs as therapeutic targets, the next step is to develop a novel antibody inhibitor that suppresses PSG expression of tumors to create a new therapy for female lung cancer patients,” Oh told Healio.
Reference:
For more information:
Jung Hun Oh, PhD, can be reached at ohj@mskcc.org.
Sources/Disclosures
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Oh JH, et al. Abstract 2398. Presented at: American Association for Cancer Research Annual Meeting; April 25-30, 2025; Chicago.
Disclosures:
Oh reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
