The prognostic role of PSMD14 in head and neck squamous cell carcinoma

Abstract

Purpose PSMD14 is an essential protein for proteasomal degradation. Inhibition of this protein disrupts homeostasis and inhibits cancer cell viability. Overexpression of PSMD14 was associated with advanced cancer characteristics and a worse prognosis in various carcinomas. This study aimed to analyze PSMD14 copy number variation, mRNA and protein expression in HNSCC, and its role as an independent prognostic biomarker. Methods PSMD14 mRNA expression and copy number variations were analyzed in “The Cancer Genome Atlas (TCGA)” in 510 patients. Protein expression was evaluated using immunohistochemistry in a second cohort including 115 patients. PSMD14 levels were analyzed for correlation with clinicopathological data, overall and disease-free survival. Results PSMD14 mRNA expression and copy number variation were high in 44 and 50% of patients, respectively. Protein expression of PSMD14 was high in 56%. In both cohorts, high PSMD14 levels were associated with advanced staging. High PSMD14 mRNA expression was additionally associated with a worse prognosis in univariable analysis. However, after correction for possible confounders, PSMD14 mRNA was not an independent prognostic marker. Conclusion PSMD14 is commonly expressed in HNSCC patients and associated with advanced stages. High expression of PSMD14 mRNA was associated with a worse outcome. However, this may be a result of the association of PSMD14 with poor prognosticators. Based on our study, further evaluation of PSMD14 as a prognostic marker and potential therapeutic target is warranted.

USP4 promotes proliferation and metastasis in human lung adenocarcinoma

“…MMP2 can also promote lymphangiogenesis and lymph node metastasis (32,33). VEGF can induce lymphangiogenesis and promote lymph node metastasis (34,35). Our study showed that in human lung adenocarcinoma, the expression of USP4 was positively correlated with the expression of VEGF and MMP2, and the probability of lymph node metastasis was higher in lung adenocarcinoma patients with high…”

Studying Antifatigue Mechanism of Tyr-Pro-Leu-Pro in Exercise Mice Using Label-Free Proteomics

“…Among 17 upregulated DAPs, the FC values of Psmd14 and alpha-Crystallin B chain (Cryab) were high. Psmd14, an important component of the 26S proteasome, could remove misfolded or damaged proteins to maintain protein homeostasis, 28 and Cryab acts as a chaperone to prevent protein aggregation under stress conditions. 29 The increase of Psmd14 and Cryab in the H-YPLP group indicated that YPLP was beneficial to maintain muscle protein homeostasis and then improve muscle function.…”

High USP4 mRNA is associated with an HPV-positive status in head and neck squamous cell carcinoma patients

“…Patient data were drawn from cBioportal.org “The Cancer Genome Atlas (TCGA), Firehose Legacy” and supplemented with “TCGA, PanCancer Atlas” (Liu et al 2018 ) and “TCGA, Nature 2015” (Lawrence et al 2015 ) as described before by Schnoell et al ( 2022 ). We included a total of 510 patients, who were treated between 1978 and 2012.…”

“…Immunohistochemistry was done following the manufacturer's protocol of the Ultra Vision Quanto Detection System HRP (Thermo Fisher Scientific, Waltham, MA, USA) with the following modifications (Schnoell et al 2022 ). Briefly, samples were deparaffinized, rehydrated and incubated in H 2 O 2 to suppress endogenous peroxidase activity.…”

“…Because of their potential to evolve tumor diagnosis and therapy, ubiquitin-specific proteases were studied extensively in the past (Vlasschaert et al 2015 ). In particular, our previous work on PSMD14 (Schnoell et al 2022 ), another member of the DUB system prompted us to investigate the role of USP4 in HNSCC. In this study, we aimed to elucidate USP4 mRNA and protein expression levels in relation to survival outcome and the association with clinicopathological aspects of HNSCC patients.…”