Comprehensive analysis of TMEM9 in human tumors

Abstract Background TMEM9, a transmembrane protein, has emerged as a significant player in tumor progression, yet its comprehensive role across various cancers remains unclear. This study investigates the expression patterns, genetic alterations, immune associations, and prognostic implications of T...

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Main Authors: Xuezhong Zhang, Lele Zhou, Shumin Wei, Xuebin Zhang
Format: Article
Language:English
Published: Springer 2025-03-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02040-1
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author Xuezhong Zhang
Lele Zhou
Shumin Wei
Xuebin Zhang
author_facet Xuezhong Zhang
Lele Zhou
Shumin Wei
Xuebin Zhang
author_sort Xuezhong Zhang
collection DOAJ
description Abstract Background TMEM9, a transmembrane protein, has emerged as a significant player in tumor progression, yet its comprehensive role across various cancers remains unclear. This study investigates the expression patterns, genetic alterations, immune associations, and prognostic implications of TMEM9 across multiple cancer types using large-scale bioinformatics approaches. Methods TMEM9 expression was analyzed in normal and tumor tissues using data from the TCGA and GTEx databases, with protein expression verified via CPTAC datasets. The prognostic impact of TMEM9 was assessed using overall survival (OS) and disease-free survival (DFS) analyses across various cancers. Genetic alterations, including mutation types and copy number alterations, were explored using the cBioPortal platform. We also examined DNA methylation, RNA modifications, and immune infiltration correlations using bioinformatics tools, including TIMER2 and UALCAN. TMEM9’s relationship with tumor mutational burden (TMB) and microsatellite instability (MSI) was analyzed, and gene enrichment analyses were performed using the STRING database and GO/KEGG pathway analyses. Results TMEM9 was significantly overexpressed in several cancers, including ACC, BLCA, BRCA, CHOL, COAD, GBM, and others. Elevated TMEM9 expression correlated with worse OS and DFS in ACC, CESC, KICH, UVM, and additional tumor types. Genetic alterations, predominantly amplifications, were frequent in BRCA, LIHC, and UCEC. DNA methylation analysis revealed hypermethylation in tumors like HNSC and KIRC, while RNA modification analyses showed TMEM9 associations with m6A and m1A-related genes. TMEM9 expression was strongly correlated with immune infiltration, particularly cancer-associated fibroblasts in tumors like THYM and HNSC. Positive associations between TMEM9 and TMB/MSI were observed in several cancers, suggesting genomic instability. Enrichment analyses identified TMEM9 involvement in pathways related to the endoplasmic reticulum, Wnt signaling, and protein processing. Conclusion TMEM9 plays a crucial role in cancer progression, influencing gene expression, immune modulation, and genomic instability. These findings highlight TMEM9 as a potential prognostic biomarker and therapeutic target across multiple cancer types.
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spelling doaj-art-e6620adf14254974b169e185186790142025-08-20T01:57:47ZengSpringerDiscover Oncology2730-60112025-03-0116111710.1007/s12672-025-02040-1Comprehensive analysis of TMEM9 in human tumorsXuezhong Zhang0Lele Zhou1Shumin Wei2Xuebin Zhang3Department of Laboratory Medicine, Zibo Central HospitalDepartment of Laboratory Medicine, Zibo Central HospitalDepartment of Anesthesiology (Operation Room),, Dongying People’s Hospital (Dongying Hospital of Shandong Provincial Hospital Group)Department of Anorectal Surgery, Dongying People’s Hospital (Dongying Hospital of Shandong Provincial Hospital Group)Abstract Background TMEM9, a transmembrane protein, has emerged as a significant player in tumor progression, yet its comprehensive role across various cancers remains unclear. This study investigates the expression patterns, genetic alterations, immune associations, and prognostic implications of TMEM9 across multiple cancer types using large-scale bioinformatics approaches. Methods TMEM9 expression was analyzed in normal and tumor tissues using data from the TCGA and GTEx databases, with protein expression verified via CPTAC datasets. The prognostic impact of TMEM9 was assessed using overall survival (OS) and disease-free survival (DFS) analyses across various cancers. Genetic alterations, including mutation types and copy number alterations, were explored using the cBioPortal platform. We also examined DNA methylation, RNA modifications, and immune infiltration correlations using bioinformatics tools, including TIMER2 and UALCAN. TMEM9’s relationship with tumor mutational burden (TMB) and microsatellite instability (MSI) was analyzed, and gene enrichment analyses were performed using the STRING database and GO/KEGG pathway analyses. Results TMEM9 was significantly overexpressed in several cancers, including ACC, BLCA, BRCA, CHOL, COAD, GBM, and others. Elevated TMEM9 expression correlated with worse OS and DFS in ACC, CESC, KICH, UVM, and additional tumor types. Genetic alterations, predominantly amplifications, were frequent in BRCA, LIHC, and UCEC. DNA methylation analysis revealed hypermethylation in tumors like HNSC and KIRC, while RNA modification analyses showed TMEM9 associations with m6A and m1A-related genes. TMEM9 expression was strongly correlated with immune infiltration, particularly cancer-associated fibroblasts in tumors like THYM and HNSC. Positive associations between TMEM9 and TMB/MSI were observed in several cancers, suggesting genomic instability. Enrichment analyses identified TMEM9 involvement in pathways related to the endoplasmic reticulum, Wnt signaling, and protein processing. Conclusion TMEM9 plays a crucial role in cancer progression, influencing gene expression, immune modulation, and genomic instability. These findings highlight TMEM9 as a potential prognostic biomarker and therapeutic target across multiple cancer types.https://doi.org/10.1007/s12672-025-02040-1TMEM9Pan-CancerTumorsTumorigenesis
spellingShingle Xuezhong Zhang
Lele Zhou
Shumin Wei
Xuebin Zhang
Comprehensive analysis of TMEM9 in human tumors
Discover Oncology
TMEM9
Pan-Cancer
Tumors
Tumorigenesis
title Comprehensive analysis of TMEM9 in human tumors
title_full Comprehensive analysis of TMEM9 in human tumors
title_fullStr Comprehensive analysis of TMEM9 in human tumors
title_full_unstemmed Comprehensive analysis of TMEM9 in human tumors
title_short Comprehensive analysis of TMEM9 in human tumors
title_sort comprehensive analysis of tmem9 in human tumors
topic TMEM9
Pan-Cancer
Tumors
Tumorigenesis
url https://doi.org/10.1007/s12672-025-02040-1
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