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Peer-reviewedCC BY-NC-ND 4.0Oncology Reports

CHCHD2 as a prognostic biomarker and therapeutic target in lung adenocarcinoma: Insights from pan-cancer multi-omics and functional studies

  • Zikai Xu1
  • Jie Shen1
  • Yizhou Lin2
  • Haotian Shi1
  • Cong Zhang1
  • Zhengwei Zhang3
  • Xiaoyu Zhou1
  • Zheng Yang1
  1. 1Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
  2. 2Medical School of Nantong University, Nantong, Jiangsu 226001, P.R. China
  3. 3Department of Pharmacy, Affiliated Hospital of Nantong University, Pharmacy School of Nantong University, Nantong, Jiangsu 226001, P.R. China
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Abstract

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, and mitochondrial proteins have been increasingly implicated in tumor progression. Coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) has been reported in several malignancies, yet its pan-cancer landscape and LUAD-specific functional relevance have not been comprehensively evaluated. In the present study, multi-omics analyses were integrated using The Cancer Genome Atlas-derived datasets and public resources [including Gene Expression Profiling Interactive Analysis (GEPIA) 2, CIBERSORT and CellMiner] to characterize CHCHD2 expression patterns, clinical associations, tumor microenvironment (TME) features, stemness-related indices and drug-response correlations across cancers, followed by experimental validation in LUAD models. CHCHD2 was found to be upregulated in multiple cancers and was correlated with advanced disease stage and poor overall survival, especially in patients with LUAD. CHCHD2 promoted cell proliferation and migration while inhibiting apoptosis. CHCHD2 knockdown reduced AKT and ERK phosphorylation and suppressed xenograft tumor growth in vivo. High CHCHD2 expression was associated with increased stemness, an immunosuppressive TME, and differential drug-response patterns in CellMiner analyses, suggesting that CHCHD2 expression may be associated with compound-specific sensitivity profiles. Collectively, these findings support an oncogenic role of CHCHD2 in LUAD and highlight its potential utility as a prognostic biomarker and therapeutic target.

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Cite

BibTeXRIS
BibTeX
@article{xu2026chchd2,
  title = {{CHCHD2 as a prognostic biomarker and therapeutic target in lung adenocarcinoma: Insights from pan-cancer multi-omics and functional studies}},
  author = {Zikai Xu and Jie Shen and Yizhou Lin and Haotian Shi and Cong Zhang and Zhengwei Zhang and Xiaoyu Zhou and Zheng Yang},
  journal = {Oncology Reports},
  year = {2026},
  month = oct,
  doi = {10.3892/or.2026.9213},
  url = {https://doi.org/10.3892/or.2026.9213},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - CHCHD2 as a prognostic biomarker and therapeutic target in lung adenocarcinoma: Insights from pan-cancer multi-omics and functional studies
AU  - Zikai Xu
AU  - Jie Shen
AU  - Yizhou Lin
AU  - Haotian Shi
AU  - Cong Zhang
AU  - Zhengwei Zhang
AU  - Xiaoyu Zhou
AU  - Zheng Yang
PY  - 2026
DA  - 2026/10/15
JO  - Oncology Reports
DO  - 10.3892/or.2026.9213
UR  - https://doi.org/10.3892/or.2026.9213
AB  - Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, and mitochondrial proteins have been increasingly implicated in tumor progression. Coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) has been reported in several malignancies, yet its pan-cancer landscape and LUAD-specific functional relevance have not been comprehensively evaluated. In the present study, multi-omics analyses were integrated using The Cancer Genome Atlas-derived datasets and public resources [including Gene Expression Profiling Interactive Analysis (GEPIA) 2, CIBERSORT and CellMiner] to characterize CHCHD2 expression patterns, clinical associations, tumor microenvironment (TME) features, stemness-related indices and drug-response correlations across cancers, followed by experimental validation in LUAD models. CHCHD2 was found to be upregulated in multiple cancers and was correlated with advanced disease stage and poor overall survival, especially in patients with LUAD. CHCHD2 promoted cell proliferation and migration while inhibiting apoptosis. CHCHD2 knockdown reduced AKT and ERK phosphorylation and suppressed xenograft tumor growth in vivo. High CHCHD2 expression was associated with increased stemness, an immunosuppressive TME, and differential drug-response patterns in CellMiner analyses, suggesting that CHCHD2 expression may be associated with compound-specific sensitivity profiles. Collectively, these findings support an oncogenic role of CHCHD2 in LUAD and highlight its potential utility as a prognostic biomarker and therapeutic target.
SN  - 1021-335X
SN  - 1791-2431
ER  -