Vol. 2 No. 5 (2025)

Research Articles

PBX/Knotted 1 homeobox 2 as a novel prognostic marker that dysregulated in lung adenocarcinoma

Published 2025-09-30

  • Lisa Sun
    • ,
  • Yuxi Ren
    • ,
  • Ping Xiao
    • ,
  • Haoming Shen
    • ,
  • Bin Qu

Lisa Sun
Hunan Cancer Hospital image/svg+xml , Central South University image/svg+xml

Yuxi Ren
Hunan Cancer Hospital image/svg+xml , Central South University image/svg+xml

Ping Xiao
Hunan Cancer Hospital image/svg+xml , Central South University image/svg+xml

Haoming Shen
Hunan Cancer Hospital image/svg+xml , Central South University image/svg+xml

Bin Qu
Hunan Cancer Hospital image/svg+xml , Central South University image/svg+xml

Abstract

Homeobox-containing genes are evolutionary conserved regulators that play important roles in embryogenesis and tumorigenesis. We started by searching differentially expressed (DE) homeobox-containing genes in lung adenocarcinoma datasets and obtained 14 candidates from a total of 238 distinct members. Using univariant Cox and lasso regression, we created a 6 DE-homeobox-containing gene-based model that successfully predicted overall survival, disease-free time survival, and progression-free intervals in LUAD patients. Following that, we notice that PKNOX2 (PBX/Knotted 1 Homeobox 2) is the most potent protective factor for overall survival of LUAD patients. Its expression was significantly downregulated in LUAD and decreased as tumor pathological grade increased. PKNOX2 was as an independent prognostic marker in LUAD in univariate and multivariate Cox proportional and further confirmed in Kaplan-Meier survival analyses. Gene Set Enrichment Analysis (GSEA) results revealed that PKNOX2 related genes were enriched in immune response as well as extracellular matrix organization. Further we revealed that PKNOX2 was linked to tumor purity and macrophage filtrations. Since previous studies suggested that PKNOX2 play a tumor suppressive role in gastric cancer, however its pathological role in LUAD is unknown. These findings suggest that PKNOX2 dysregulation may play a role in the development of LUAD tumors and could be used as a novel prognostic marker for LUAD patients.

Keywords

PBX/Knotted 1 homeobox 2, Lung Adenocarcinoma, Homeobox Genes, Prognostic Marker

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