Abstract
Recently, it was reported that ubiquilin 4 (UBQLN4) alteration was associated with genomic instability in some cancers. However, whether UBQLN4 is a valuable biomarker for the prognosis of immunotherapy in pan-cancer was not identified. We evaluated the biologic and oncologic significance of UBQLN4 in pan-cancer at multiomics level, such as expression, mutation, copy number variation (CNV), methylation, and N6-methyladenosine (m6A) methylation. These omics data were obtained from several public databases, including Oncomine, The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), the Genotype-Tissue Expression (GTEx), the Human Protein Atlas (HPA), Gene Set Cancer Analysis (GSCA), m6A-Atlas, CancerSEA, and RNAactDrug. We found that UBQLN4 mRNA and protein were overexpressed in most cancer types, and the expression, mutation, CNV, and methylation of UBQLN4 were associated with the prognosis of some cancers. Mechanistically, UBQLN4 was involved in angiogenesis, DNA damage, apoptosis, and the pathway of PI3K/AKT and TSC/mTOR. Moreover, UBQLN4 mRNA was significantly correlated with immune checkpoints, tumor mutational burden (TMB), microsatellite instability (MSI), and mismatch repair (MMR). And, the correlation among UBQLN4 mRNA, CNV, and methylation and immune microenvironment was also identified. Furthermore, UBQLN4 was associated with the sensitivity of chemotherapy and targeted drugs at multiomics level. In conclusion, UBQLN4 was a promising prognostic biomarker of immune-related therapy in pan-cancer.
Highlights
Ubiquilin 4 (UBQLN4) is a member of UBQLNs family, which could bind proteasome subunits and ubiquitin proteins to degrade proteasome through its ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains, respectively [1]
We downloaded the latest data of e Cancer Genome Atlas (TCGA) of UBQLN4 RNA-sequencing, somatic mutation, and related clinical data in 33 types of cancer via UCSC Xena platform [10]. e clinical data included overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) data of patients with 33 cancers. e detailed abbreviations of 33 cancer types are included in Supplementary Table 1
UBQLN4 mRNA Expression Profile in Pan-Cancer Based on Different Databases
Summary
Ubiquilin 4 (UBQLN4) is a member of UBQLNs family, which could bind proteasome subunits and ubiquitin proteins to degrade proteasome through its ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains, respectively [1]. Studies primarily focused on the role of UBQLN4 in maintaining protein homeostasis [2, 3]. The role of UBQLN4 in cancers attracted increasing attention [6, 7], theories behind are premature. It was reported that the increase of UBQLN4 in neuroblastoma and melanoma decreased survival [4]. Yan Yu et al found that UBQLN4 promoted the proliferation and invasion of hepatocellular carcinoma cells by activating wnt-β-catenin pathway [8]. Shengkai Huang et al revealed that the overexpression of UBQLN4 induced G1/S cell cycle arrest and activated p53/p21 axis, inhibiting the proliferation of gastric cancer cells [9]. The overexpression of UBQLN4 was reported to upregulate the sensitivity of PARP1 inhibitors [4]
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