Nikhil Prasad Fact checked by:Thailand Medical News Team Feb 15, 2026 1 hour, 27 minutes ago
Medical News: A major new scientific investigation has uncovered surprising evidence that progesterone receptors—proteins normally associated with reproductive biology—may play a critical role in determining how aggressive and deadly head and neck cancers become. The findings could help doctors predict which patients face worse outcomes and may open the door to more personalized treatments in the future. This
Medical News report highlights how hormone-related mechanisms may influence cancers.
Hormone Receptors Linked to Deadlier Head and Neck Cancers
Researchers Examine Hormone Receptors in Tumor Samples
The study was conducted by scientists from the Laboratory for Hereditary Cancer and the Laboratory of Molecular Virology and Bacteriology at the Ruđer Bošković Institute in Zagreb, Croatia, the Department of Otolaryngology and Department of Oncology at University Hospital Centre Zagreb, the Department of Maxillofacial and Oral Surgery at University Hospital Osijek, the Faculty of Medicine Osijek at Josip Juraj Strossmayer University of Osijek, and Bexorg Inc. in New Haven, USA.
Researchers analyzed tissue samples from 160 individuals, including 95 patients with primary head and neck squamous cell carcinoma, 25 metastatic lymph node samples, and 40 healthy oral tissue samples. They focused on progesterone receptors, including both nuclear progesterone receptors (PGR) and membrane progesterone receptors such as PAQR5, PAQR6, PAQR7, PAQR8, PAQR9, PGRMC1, and PGRMC2.
These receptors act like molecular switches inside cells, responding to the hormone progesterone and influencing gene activity, cell growth, and survival.
Dangerous Patterns Linked to Aggressive Tumors
One of the most important discoveries was that certain progesterone receptor genes behaved very differently in cancerous tissue compared to healthy tissue. Specifically, the PGR gene showed increased activity in metastatic lymph nodes, suggesting a role in helping cancer spread beyond its original site.
At the same time, several membrane receptors—including PAQR5, PAQR7, PAQR8, and PAQR9—were reduced in primary tumors. However, paradoxically, higher expression of some of these receptors in specific cases was linked to more aggressive disease.
For example, tumors that showed higher levels of PAQR5 and PAQR7 were strongly associated with poorer survival rates. Patients with elevated PAQR5 levels had nearly three times the risk of dying compared to patients with lower levels.
Older Patients and Advanced Tumors Show Higher Receptor Activity
The study also found that progesterone receptor expression increased significantly with age. Older patients had higher levels of several receptors, including PAQR5, PAQR6, PAQR7, PAQR9, PGRMC1, and PGRMC2.
More advanced tumors, especially large and invasive stage pT4 cancers, also showed higher levels of certain receptors such as PAQR8 and PAQR9. These tumors are known to invade nearby tissues
and are associated with worse outcomes.
In addition, tumors showing aggressive features such as perineural invasion—where cancer spreads along nerves—had significantly increased PAQR5 expression, highlighting its potential role in helping tumors invade critical structures.
Hormone Biology May Explain Gender Differences in Cancer Risk
Head and neck cancers occur far more frequently in men than women. Scientists have long suspected that hormones might influence this difference. The new findings strengthen this theory, showing that progesterone receptor activity varies by sex and may affect tumor behavior.
Interestingly, female patients showed higher expression of certain receptors such as PAQR8 and PAQR9, suggesting that hormonal signaling pathways may influence cancer biology differently between men and women.
These discoveries indicate that hormone-related pathways may be an overlooked factor in cancer development and progression.
New Biomarkers Could Help Predict Patient Survival
The researchers believe progesterone receptors could serve as valuable biomarkers—biological indicators that help predict how aggressive a cancer will be.
Higher expression of PAQR5 and PAQR7 was associated with shorter survival times. Patients with advanced lymph node involvement also showed significantly increased risk of death.
Identifying these markers early could allow doctors to identify high-risk patients sooner and tailor treatment strategies accordingly.
Conclusion
This groundbreaking research reveals that progesterone receptors, previously overlooked in head and neck cancers, play an important role in tumor progression, invasion, and patient survival. These hormone-related proteins appear to influence how aggressive tumors become and how likely they are to spread or resist treatment. The findings suggest that measuring progesterone receptor activity could help doctors identify high-risk patients earlier and personalize therapies. In the future, targeting these hormone pathways may even lead to new treatments that slow tumor growth, prevent metastasis, and improve survival rates for patients facing these dangerous cancers.
The study findings were published in the peer reviewed International Journal of Molecular Sciences.
https://www.mdpi.com/1422-0067/27/4/1853
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