PSMD9 expression correlates with recurrence after radiotherapy in patients with cervical cancer

Frank Köster; Lisa Sauer; Friederike Hoellen; Julika Ribbat-Idel; Karen Bräutigam; Achim Rody; Constanze Banz-Jansen

doi:10.3892/ol.2020.11622

PSMD9 expression correlates with recurrence after radiotherapy in patients with cervical cancer

Oncol Lett. 2020 Jul;20(1):581-588. doi: 10.3892/ol.2020.11622. Epub 2020 May 14.

Authors

Frank Köster¹, Lisa Sauer¹, Friederike Hoellen¹, Julika Ribbat-Idel², Karen Bräutigam¹, Achim Rody¹, Constanze Banz-Jansen³

Affiliations

¹ Department of Gynecology and Obstetrics, University of Lübeck and University Medical Center Schleswig-Holstein, Campus Lübeck, D-23538 Lübeck, Germany.
² Institute of Pathology, University of Lübeck and University Medical Center Schleswig-Holstein, Campus Lübeck, D-23538 Lübeck, Germany.
³ Department of Gynecology and Obstetrics, Evangelisches Krankenhaus Bethel, D-33617 Bielefeld, Germany.

Abstract

In the current retrospective cohort study, the expression of the Proteasome 26S non-ATPase Subunit 9 (PSMD9) was investigated in 102 patients with cervical cancer. The rat homologue of PSMD9, Bridge-1, was identified as a binding protein of the transcription factors PDX-1 and E-12 via its PDZ-domain. The aim of the current study was to evaluate the prognostic or predictive value of PSMD9 expression as a biomarker for patients with cervical cancer. Tissue microarrays were constructed from formalin-fixed paraffin-embedded tissue specimens of cervical cancer and peritumoral stroma after hysterectomy and a Bridge-1 antibody was used to perform immunohistochemistry. The immunoreactions were analyzed using an immunoreactive score, which evaluated the number of positive cells as well as their intensity of PSMD9 expression. A misinterpretation of statistically significant results after multiple testing was controlled by the false discovery rate correction using the algorithm of Benjamini and Hochberg. All tumor tissues and almost all peritumoral stroma tissues expressed PSMD9. The PSMD9 expression in tumor tissues was significantly higher compared with the peritumoral stroma. PSMD9 expression correlated significantly with the expression of the proliferation marker MIB-1. Patients with stronger PSMD9 expression tended to exhibit a higher odds ratio for the recurrence of the disease in all patients (n=102) as well as in the subgroup of 47 patients having received a combined chemoradiotherapy following hysterectomy. In the group of 62 patients having that received radiotherapy following hysterectomy, which included the chemoradiotherapy patients, a higher PSMD9 expression significantly increased the odds for a recurrence to 1.983-fold even after FDR correction (P=0.0304). In conclusion, PSMD9 was indicated to be overexpressed in tumor tissues and associated with tumor cell proliferation. Therefore, PSMD9 may be useful as a tumor marker. Furthermore, increased PSMD9 overexpression may be used to predict resistance against radiation.

Keywords: Proteasome 26S non-ATPase Subunit 9; cervical cancer; chemoradiotherapy; immunohistochemistry; radiotherapy.