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

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.

Enhancer RNA promotes resistance to radiotherapy in bone-metastatic prostate cancer by m6A modification

“…We also found that PSMD9 was a specific bone-mPCa-related gene, but WDR66 , SETD1B, and MLXIP were oncogenic genes (Figure 2 D). PSMD9 is related to 26S proteasome expression and could predict RT benefits in breast cancer 53 , 54 . Higher levels of PSMD9 were associated with lower recurrence-free survival after RT (Figure 2 E), which was consistent with the association of PSMD9 with disease-free survival in TCGA data ( Figure S2 E).…”

Panels of mRNAs and miRNAs for decoding molecular mechanisms of Renal Cell Carcinoma (RCC) subtypes utilizing Artificial Intelligence approaches

“…The PSMD9, as a part of the 26S proteasome, regulates protein degradation 52 . The PSMD9 is overexpressed in tumor tissues and associated with cell proliferation, hostile tumor outcome, and resistance to the therapy 53 – 55 . Since different tumor suppressors and oncogenes are controlled by the Ub- and proteosome-mediated degradation, the CSN7A, UBAC1, PSMD9, and RNF40 may play important roles in the pathogenesis of the KIRC.…”

PSMD8 can serve as potential biomarker and therapeutic target of the PSMD family based on bioinformatics analysis and in vitro validation

“…It was highly expressed in invasive bladder cancer and breast cancer [45][46]. High expression of PSMD9 was associated with post-radiotherapy recurrence in cervical and breast cancer [47], and endogenous PSMD10 interacted with GRP78 to regulate endoplasmic reticulum stress, which might provide a therapeutic target for homocysteine-induced liver injury [48]. miR-3619-5p inhibited tumor growth in vivo by inducing the phosphorylation of activator of transcription 3 (STAT3) and retinoblastoma protein (Rb1), thereby targeting PSMD10 to inhibit cell proliferation and induce G1 arrest [49].…”