Evidence map›Paper›PMID 42269569›Full record

ArticleTranslational oncology2026

Telomerase-related gene EHHADH drives lung cancer progression and shapes the immunosuppressive tumor microenvironment.

Wei Wei, Yuheng Wang, Diliyaer Abudukeremu, Jinhua Luo, Mingjun Du

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Article in Translational oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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5 authors.

Wei WeiDepartment of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
Yuheng WangDepartment of Thoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Diliyaer AbudukeremuTianjin Medical University , Tianjin, China.
Jinhua LuoDepartment of Thoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China. Electronic address: Ljhua1966@126.com.
Mingjun DuDepartment of Thoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China. Electronic address: dumingjun1989@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLung cancer is a leading cause of cancer-related mortality, necessitating accurate prognostic assessment and optimized treatment. Telomerase-related genes are pivotal in tumor development, yet their prognostic value and mechanisms within the lung cancer tumor microenvironment (TME) remain unclear.

methodsWe analyzed telomerase-related gene mutations in lung cancer (TCGA) and identified eight key prognostic genes (INMT, ALDH3A2, OGDHL, TDO2, EFNA3, STAT1, EHHADH, AANAT) from seven public datasets via Cox regression. A robust prognostic risk model was built and validated across independent cohorts. TME associations were explored using IPS, ESTIMATE scores, and immune infiltration analyses. EHHADH's functional role was validated via immunohistochemistry, in vitro knockdown, and single-cell RNA sequencing.

resultsOur model demonstrated strong predictive performance and consistently outperformed existing prognostic signatures across multiple datasets. Importantly, low-risk patients exhibited an "immune-hot" phenotype with higher IPS scores and enhanced immune cell infiltration, suggesting potential sensitivity to immunotherapy. In contrast, high-risk patients displayed an immunosuppressive microenvironment. Among the model genes, EHHADH emerged as a key oncogenic driver, positively associated with risk score and poor survival. Functional assays revealed that EHHADH promotes tumor cell migration while reducing adhesion. Single-cell analysis further demonstrated that EHHADH is predominantly expressed in epithelial cells and is associated with an "immune-desert" TME characterized by reduced immune infiltration.

conclusionThis study establishes a clinically relevant telomerase-related gene signature that enables effective risk stratification and provides insights into tumor-immune interactions in lung cancer. Notably, EHHADH is identified as a potential therapeutic target that contributes to immune evasion and tumor progression. These findings offer a foundation for personalized prognostic assessment and suggest that targeting EHHADH may enhance the efficacy of immunotherapy in lung cancer patients.

Indexed as

EHHADHLung adenocarcinomaPrognostic modelTelomeraseTumor microenvironment

Identifiers

PMID42269569
PMCPMC13272562

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