TM9SF4 is a potential prognostic biomarker in hepatocellular carcinoma

Abstract Background The transmembrane 9 superfamily protein member 4 (TM9SF4) is a transmembrane protein upregulated in multiple cancers; however, its role in hepatocellular carcinoma (HCC) remains unknown. Methods The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and International C...

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Main Authors: Yahui Ma, Lingling Guo, Bo Zhang, Ting Wang, Qingchun Feng
Format: Article
Language:English
Published: Springer 2025-04-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02417-2
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author Yahui Ma
Lingling Guo
Bo Zhang
Ting Wang
Qingchun Feng
author_facet Yahui Ma
Lingling Guo
Bo Zhang
Ting Wang
Qingchun Feng
author_sort Yahui Ma
collection DOAJ
description Abstract Background The transmembrane 9 superfamily protein member 4 (TM9SF4) is a transmembrane protein upregulated in multiple cancers; however, its role in hepatocellular carcinoma (HCC) remains unknown. Methods The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and International Cancer Genome Consortium (ICGC) databases were utilized to investigate the differential expression of TM9SF4 in HCC and tumor tissues. The prognostic and value of TM9SF4 in HCC was evaluated using Kaplan–Meier analysis, Cox regression, and receiver operating characteristic (ROC) curve analyses. The expression pattern and prognostic value of TM9SF4 was further verified using immunohistochemical (IHC) examination of 87 pairs of HCC clinical specimens. A nomogram was constructed by combining TM9SF4 expression and clinicopathological parameters to predict prognosis for individual patient. Additionally, gene set enrichment analysis (GSEA) was performed to identify key pathways related to TM9SF4. Results TM9SF4 expression was upregulated in the HCC tissues. High expression of TM9SF4 was significantly associated with advanced T stage, histological grade, and worse survival. Multivariable Cox analysis revealed that TM9SF4 expression was an independent factor for overall survival. The nomogram by incorporating the TM9SF4 and T stage showed good performance in predicting prognosis. Moreover, GSEA analysis revealed that TM9SF4 was functionally involved in pathways associated with the cell cycle. Conclusions These findings suggest that TM9SF4 is a promising biomarker with prognostic potential and functional significance in HCC.
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spelling doaj-art-1d2697eeff7c47d4ba7f9b7dda23f3ba2025-08-20T02:19:58ZengSpringerDiscover Oncology2730-60112025-04-0116111010.1007/s12672-025-02417-2TM9SF4 is a potential prognostic biomarker in hepatocellular carcinomaYahui Ma0Lingling Guo1Bo Zhang2Ting Wang3Qingchun Feng4Department of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health SciencesDepartment of Radiation Oncology, Peking University Shenzhen HospitalDepartment of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health SciencesDepartment of Hepatobiliary and Pancreatic Surgery, Peking University Shenzhen HospitalDepartment of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health SciencesAbstract Background The transmembrane 9 superfamily protein member 4 (TM9SF4) is a transmembrane protein upregulated in multiple cancers; however, its role in hepatocellular carcinoma (HCC) remains unknown. Methods The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and International Cancer Genome Consortium (ICGC) databases were utilized to investigate the differential expression of TM9SF4 in HCC and tumor tissues. The prognostic and value of TM9SF4 in HCC was evaluated using Kaplan–Meier analysis, Cox regression, and receiver operating characteristic (ROC) curve analyses. The expression pattern and prognostic value of TM9SF4 was further verified using immunohistochemical (IHC) examination of 87 pairs of HCC clinical specimens. A nomogram was constructed by combining TM9SF4 expression and clinicopathological parameters to predict prognosis for individual patient. Additionally, gene set enrichment analysis (GSEA) was performed to identify key pathways related to TM9SF4. Results TM9SF4 expression was upregulated in the HCC tissues. High expression of TM9SF4 was significantly associated with advanced T stage, histological grade, and worse survival. Multivariable Cox analysis revealed that TM9SF4 expression was an independent factor for overall survival. The nomogram by incorporating the TM9SF4 and T stage showed good performance in predicting prognosis. Moreover, GSEA analysis revealed that TM9SF4 was functionally involved in pathways associated with the cell cycle. Conclusions These findings suggest that TM9SF4 is a promising biomarker with prognostic potential and functional significance in HCC.https://doi.org/10.1007/s12672-025-02417-2Hepatocellular carcinomaTM9SF4Prognosis predictionCell cycle
spellingShingle Yahui Ma
Lingling Guo
Bo Zhang
Ting Wang
Qingchun Feng
TM9SF4 is a potential prognostic biomarker in hepatocellular carcinoma
Discover Oncology
Hepatocellular carcinoma
TM9SF4
Prognosis prediction
Cell cycle
title TM9SF4 is a potential prognostic biomarker in hepatocellular carcinoma
title_full TM9SF4 is a potential prognostic biomarker in hepatocellular carcinoma
title_fullStr TM9SF4 is a potential prognostic biomarker in hepatocellular carcinoma
title_full_unstemmed TM9SF4 is a potential prognostic biomarker in hepatocellular carcinoma
title_short TM9SF4 is a potential prognostic biomarker in hepatocellular carcinoma
title_sort tm9sf4 is a potential prognostic biomarker in hepatocellular carcinoma
topic Hepatocellular carcinoma
TM9SF4
Prognosis prediction
Cell cycle
url https://doi.org/10.1007/s12672-025-02417-2
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AT bozhang tm9sf4isapotentialprognosticbiomarkerinhepatocellularcarcinoma
AT tingwang tm9sf4isapotentialprognosticbiomarkerinhepatocellularcarcinoma
AT qingchunfeng tm9sf4isapotentialprognosticbiomarkerinhepatocellularcarcinoma