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Peer-reviewedCC BYGenes

Histology-Stratified Clinical and Prognostic Associations of PDCD-Related Genes in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma.

  1. 1Medical Course, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea.
  2. 2Department of Anatomy, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea.

Abstract

Background

The prognostic relevance of PDCD-related genes in non-small cell lung cancer remains uncertain. We examined PDCD2, PDCD4, PDCD5, PDCD10, and AVEN separately in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC).Methods

Matched TCGA expression cohorts comprised 492 LUAD and 484 LUSC tumors. Primary Cox models evaluated continuous expression per standard deviation using separate gene-specific models adjusted for age, sex, smoking history, and pathologic stage. Benjamini-Hochberg correction covered ten gene-histology tests. Proportional hazards, multicollinearity, model specification, and the incremental value of PDCD4 were assessed. GSE30219 provided 83 LUAD and 61 LUSC patients for unadjusted and clinically adjusted external analyses. Hallmark enrichment was evaluated using legacy RSEM expression and a STAR TPM sensitivity analysis.Results

The primary TCGA models included 469 LUAD patients with 167 deaths and 467 LUSC patients with 205 deaths. AVEN was associated with poorer LUAD survival after correction (HR 1.272, 95% CI 1.091-1.483; q = 0.022). PDCD4 was not significant in the primary LUAD model (HR 0.875, 95% CI 0.749-1.021; q = 0.150). Adding PDCD4 to clinical variables yielded a C-index increase of 0.014 (bootstrap 95% CI -0.004 to 0.031). No adjusted external association survived correction. PDCD4-associated enrichment differed between expression pipelines.Conclusions

AVEN showed an exploratory adverse association in TCGA LUAD, but external prognostic replication was not established. These analyses do not support a robust independent prognostic claim for PDCD4 or the clinical use of any of the five evaluated genes.

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BibTeX
@article{kim2026histologystratified,
  title = {{Histology-Stratified Clinical and Prognostic Associations of PDCD-Related Genes in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma.}},
  author = {Seong-Tae Kim and Yunha Lee and Se-Young Yun and Jin-Woo Min and Eun-Chan Jeon and Se-Hyun Kim and Jin-Sub Yoo and Se-Jin Park and Ji-Hwan Jung and Jun-Chae Lee and Jae-Ho Lee},
  journal = {Genes},
  year = {2026},
  month = oct,
  doi = {10.3390/genes17101238},
  url = {https://europepmc.org/article/MED/42938354},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Histology-Stratified Clinical and Prognostic Associations of PDCD-Related Genes in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma.
AU  - Seong-Tae Kim
AU  - Yunha Lee
AU  - Se-Young Yun
AU  - Jin-Woo Min
AU  - Eun-Chan Jeon
AU  - Se-Hyun Kim
AU  - Jin-Sub Yoo
AU  - Se-Jin Park
AU  - Ji-Hwan Jung
AU  - Jun-Chae Lee
AU  - Jae-Ho Lee
PY  - 2026
DA  - 2026/10/08
JO  - Genes
DO  - 10.3390/genes17101238
UR  - https://europepmc.org/article/MED/42938354
AB  - Background  The prognostic relevance of PDCD-related genes in non-small cell lung cancer remains uncertain. We examined PDCD2, PDCD4, PDCD5, PDCD10, and AVEN separately in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC).Methods  Matched TCGA expression cohorts comprised 492 LUAD and 484 LUSC tumors. Primary Cox models evaluated continuous expression per standard deviation using separate gene-specific models adjusted for age, sex, smoking history, and pathologic stage. Benjamini-Hochberg correction covered ten gene-histology tests. Proportional hazards, multicollinearity, model specification, and the incremental value of PDCD4 were assessed. GSE30219 provided 83 LUAD and 61 LUSC patients for unadjusted and clinically adjusted external analyses. Hallmark enrichment was evaluated using legacy RSEM expression and a STAR TPM sensitivity analysis.Results  The primary TCGA models included 469 LUAD patients with 167 deaths and 467 LUSC patients with 205 deaths. AVEN was associated with poorer LUAD survival after correction (HR 1.272, 95% CI 1.091-1.483; q = 0.022). PDCD4 was not significant in the primary LUAD model (HR 0.875, 95% CI 0.749-1.021; q = 0.150). Adding PDCD4 to clinical variables yielded a C-index increase of 0.014 (bootstrap 95% CI -0.004 to 0.031). No adjusted external association survived correction. PDCD4-associated enrichment differed between expression pipelines.Conclusions  AVEN showed an exploratory adverse association in TCGA LUAD, but external prognostic replication was not established. These analyses do not support a robust independent prognostic claim for PDCD4 or the clinical use of any of the five evaluated genes.
SN  - 2073-4425
ER  -