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Peer-reviewedCC BY-NC-NDThe journal of gene medicine

Pan-Cancer Landscape of TMEM9 With Experimental Validation in Head and Neck Squamous Cell Carcinoma.

4 affiliations
  1. 1Department of Emergency, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, Zhejiang, China.
  2. 2Internal Medicine of Traditional Chinese Medicine, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, Zhejiang, China.
  3. 3Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China.
  4. 4Department of Rehabilitation, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, Zhejiang, China.

Abstract

Background

Transmembrane protein 9 (TMEM9) has been implicated in tumor progression, but its pan-cancer diagnostic, prognostic, and immunological relevance remains incompletely characterized.Methods

TMEM9 expression, diagnostic and prognostic value, genetic alterations, functional states, and immune associations were systematically evaluated using TCGA, GTEx, and complementary public cancer databases. Experimental validation was primarily performed in HNSC models using Western blotting, colony-formation, wound-healing, Transwell, and xenograft assays, with additional exploratory validation in RCC models.Results

TMEM9 showed good-to-high diagnostic performance in 15 evaluable cancer cohorts, with particularly high AUCs in CHOL (1.000), KICH (0.970), LIHC (0.949), and THYM (0.925), whereas BRCA also showed strong discriminatory performance (AUC = 0.890). Higher TMEM9 expression was associated with unfavorable survival in several cancers, although its prognostic relevance varied by tumor type. TMEM9 expression was also associated with cancer-related pathways, functional states, immune cell infiltration, and immunoregulatory gene expression in a context-dependent manner. Experimentally, TMEM9 knockdown suppressed colony formation, wound closure, migration, and invasion in HNSC cells and inhibited FaDu xenograft growth. Similar inhibitory effects were additionally observed in exploratory RCC models.Conclusion

TMEM9 exhibits cancer-type-dependent diagnostic, prognostic, and immunological associations, whereas functional experiments support a tumor-promoting role for TMEM9 in HNSC. Exploratory RCC experiments suggest that this effect may also occur in selected renal cancer cellular contexts.

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BibTeX
@article{wang2026pancancer,
  title = {{Pan-Cancer Landscape of TMEM9 With Experimental Validation in Head and Neck Squamous Cell Carcinoma.}},
  author = {Mi Wang and Shangyan Ying and Chunyan Weng and Youfeng Li},
  journal = {The journal of gene medicine},
  year = {2026},
  month = oct,
  doi = {10.1002/jgm.70117},
  url = {https://europepmc.org/article/MED/42952125},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Pan-Cancer Landscape of TMEM9 With Experimental Validation in Head and Neck Squamous Cell Carcinoma.
AU  - Mi Wang
AU  - Shangyan Ying
AU  - Chunyan Weng
AU  - Youfeng Li
PY  - 2026
DA  - 2026/10/28
JO  - The journal of gene medicine
DO  - 10.1002/jgm.70117
UR  - https://europepmc.org/article/MED/42952125
AB  - Background  Transmembrane protein 9 (TMEM9) has been implicated in tumor progression, but its pan-cancer diagnostic, prognostic, and immunological relevance remains incompletely characterized.Methods  TMEM9 expression, diagnostic and prognostic value, genetic alterations, functional states, and immune associations were systematically evaluated using TCGA, GTEx, and complementary public cancer databases. Experimental validation was primarily performed in HNSC models using Western blotting, colony-formation, wound-healing, Transwell, and xenograft assays, with additional exploratory validation in RCC models.Results  TMEM9 showed good-to-high diagnostic performance in 15 evaluable cancer cohorts, with particularly high AUCs in CHOL (1.000), KICH (0.970), LIHC (0.949), and THYM (0.925), whereas BRCA also showed strong discriminatory performance (AUC = 0.890). Higher TMEM9 expression was associated with unfavorable survival in several cancers, although its prognostic relevance varied by tumor type. TMEM9 expression was also associated with cancer-related pathways, functional states, immune cell infiltration, and immunoregulatory gene expression in a context-dependent manner. Experimentally, TMEM9 knockdown suppressed colony formation, wound closure, migration, and invasion in HNSC cells and inhibited FaDu xenograft growth. Similar inhibitory effects were additionally observed in exploratory RCC models.Conclusion  TMEM9 exhibits cancer-type-dependent diagnostic, prognostic, and immunological associations, whereas functional experiments support a tumor-promoting role for TMEM9 in HNSC. Exploratory RCC experiments suggest that this effect may also occur in selected renal cancer cellular contexts.
SN  - 1099-498X
SN  - 1521-2254
ER  -