PSMD9 expression predicts radiotherapy response in breast cancer

Area of Science:

• Oncology
• Radiotherapy
• Molecular Biology

Background:

• Radiotherapy is recommended for over 50% of cancer patients, but treatment decisions often lack intrinsic tumor radio-sensitivity markers.
• Predictive markers could optimize radiotherapy, reducing overtreatment and improving outcomes.
• Previous studies suggested low 26S proteasome expression correlates with radio-resistance, but this is contradicted by proteasome inhibitor use.

Purpose of the Study:

• To analyze the relevance of 26S proteasome subunit PSMD9 expression in a large breast cancer cohort.
• To investigate the functional role of PSMD9 in tumor radio-sensitivity.
• To clarify conflicting reports on proteasome expression and radiotherapy response.

Main Methods:

• Immunohistochemistry was used to examine PSMD9 expression in 157 breast cancer patients.
• Kaplan-Meier and Cox regression analyses assessed PSMD9 as a prognostic and predictive marker.
• siRNA knock-downs and colony formation assays in MCF7 and MDA-MB-231 cell lines evaluated PSMD9's functional role in radio-sensitivity.

Main Results:

• Low PSMD9 expression was significantly associated with reduced local recurrence in patients receiving radiotherapy.
• This association was not observed in patients not treated with radiotherapy, suggesting PSMD9 predicts radiotherapy response.
• In vitro studies showed that reducing PSMD9 expression sensitized breast cancer cells to radiotherapy.

Conclusions:

• PSMD9 expression may predict radiotherapy benefit, with low expression indicating relative radio-sensitivity.
• This finding is opposite to previous reports on 26S proteasome expression and radiotherapy response.
• PSMD9 is highlighted as a potential therapeutic target for radio-sensitizing drugs, aligning with proteasome inhibitor use.