An integrative pan-cancer analysis of USP37 and functional validation in pancreatic cancer

BackgroundUSP37, a versatile deubiquitinase, plays a pivotal role in numerous cellular functions. Although its involvement in cancer development is well-established, the comprehensive pan-cancer analysis of USP37 remains relatively uncharted.MethodsRNA sequencing data from both normal and cancerous...

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Main Authors: Jiafei Chen, Liang Lin, Dongxing Chen, Jingui Wang, Wuhan Zhou
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1659747/full
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author Jiafei Chen
Jiafei Chen
Liang Lin
Dongxing Chen
Jingui Wang
Wuhan Zhou
author_facet Jiafei Chen
Jiafei Chen
Liang Lin
Dongxing Chen
Jingui Wang
Wuhan Zhou
author_sort Jiafei Chen
collection DOAJ
description BackgroundUSP37, a versatile deubiquitinase, plays a pivotal role in numerous cellular functions. Although its involvement in cancer development is well-established, the comprehensive pan-cancer analysis of USP37 remains relatively uncharted.MethodsRNA sequencing data from both normal and cancerous tissues were retrieved from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Genomic alterations in USP37 across multiple cancer types were examined using cBioPortal. Protein-related information on USP37 was sourced from the Human Protein Atlas (HPA) and Protein-Protein Interaction (PPI) databases. Additionally, Western blotting was conducted to evaluate USP37 expression in clinical samples and pancreatic cancer cell lines. The prognostic relevance of USP37 across various cancers was analyzed using univariate Cox regression and Kaplan–Meier survival curves. Gene Set Enrichment Analysis (GSEA) was performed to identify cancer hallmarks associated with USP37. USP37 protein levels were quantified via immunoblotting, and in vitro and in vivo functional assays were employed to assess its role in the proliferation of pancreatic cancer cells.ResultsUSP37 was found to be aberrantly expressed in several tumor types, with significant association with poor prognosis in certain cancers, including pancreatic cancer. Its expression was also strongly correlated with immune regulators, tumor mutational burden (TMB), and microsatellite instability (MSI), highlighting its potential as a predictive marker for immunotherapy outcomes. Functional assays demonstrated that USP37 fosters proliferation, migration, and invasion in pancreatic cancer cells, further underscoring its role as an oncogene.ConclusionUSP37 holds promise as a biomarker and therapeutic target in clinical oncology, providing new insights into its function in cancer.
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spelling doaj-art-4d3e2871e26841a4bc2d33c6876dff8e2025-08-25T05:26:16ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-08-011310.3389/fcell.2025.16597471659747An integrative pan-cancer analysis of USP37 and functional validation in pancreatic cancerJiafei Chen0Jiafei Chen1Liang Lin2Dongxing Chen3Jingui Wang4Wuhan Zhou5The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, ChinaDepartment of Hepatobiliary Surgery, The First Hospital of Putian City, Chengxiang, Fujian, ChinaDepartment of Hepatobiliary Surgery, The First Hospital of Putian City, Chengxiang, Fujian, ChinaDepartment of Hepatobiliary Surgery, The First Hospital of Putian City, Chengxiang, Fujian, ChinaDepartment of Hepatobiliary Surgery, The First Hospital of Putian City, Chengxiang, Fujian, ChinaDepartment of Hepatobiliary Surgery, The First Hospital of Putian City, Chengxiang, Fujian, ChinaBackgroundUSP37, a versatile deubiquitinase, plays a pivotal role in numerous cellular functions. Although its involvement in cancer development is well-established, the comprehensive pan-cancer analysis of USP37 remains relatively uncharted.MethodsRNA sequencing data from both normal and cancerous tissues were retrieved from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Genomic alterations in USP37 across multiple cancer types were examined using cBioPortal. Protein-related information on USP37 was sourced from the Human Protein Atlas (HPA) and Protein-Protein Interaction (PPI) databases. Additionally, Western blotting was conducted to evaluate USP37 expression in clinical samples and pancreatic cancer cell lines. The prognostic relevance of USP37 across various cancers was analyzed using univariate Cox regression and Kaplan–Meier survival curves. Gene Set Enrichment Analysis (GSEA) was performed to identify cancer hallmarks associated with USP37. USP37 protein levels were quantified via immunoblotting, and in vitro and in vivo functional assays were employed to assess its role in the proliferation of pancreatic cancer cells.ResultsUSP37 was found to be aberrantly expressed in several tumor types, with significant association with poor prognosis in certain cancers, including pancreatic cancer. Its expression was also strongly correlated with immune regulators, tumor mutational burden (TMB), and microsatellite instability (MSI), highlighting its potential as a predictive marker for immunotherapy outcomes. Functional assays demonstrated that USP37 fosters proliferation, migration, and invasion in pancreatic cancer cells, further underscoring its role as an oncogene.ConclusionUSP37 holds promise as a biomarker and therapeutic target in clinical oncology, providing new insights into its function in cancer.https://www.frontiersin.org/articles/10.3389/fcell.2025.1659747/fullUSP37pan-cancerpancreatic cancerprognosisbiomarker
spellingShingle Jiafei Chen
Jiafei Chen
Liang Lin
Dongxing Chen
Jingui Wang
Wuhan Zhou
An integrative pan-cancer analysis of USP37 and functional validation in pancreatic cancer
Frontiers in Cell and Developmental Biology
USP37
pan-cancer
pancreatic cancer
prognosis
biomarker
title An integrative pan-cancer analysis of USP37 and functional validation in pancreatic cancer
title_full An integrative pan-cancer analysis of USP37 and functional validation in pancreatic cancer
title_fullStr An integrative pan-cancer analysis of USP37 and functional validation in pancreatic cancer
title_full_unstemmed An integrative pan-cancer analysis of USP37 and functional validation in pancreatic cancer
title_short An integrative pan-cancer analysis of USP37 and functional validation in pancreatic cancer
title_sort integrative pan cancer analysis of usp37 and functional validation in pancreatic cancer
topic USP37
pan-cancer
pancreatic cancer
prognosis
biomarker
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1659747/full
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