POU2F3 expression in lung squamous cell carcinoma: transcriptomic and immunohistochemical profiling with prognosis

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Lung squamous cell carcinoma (LUSC) lacks specific molecular targets.
• POU class 2 homeobox 3 (POU2F3) is a transcription factor associated with tuft cells.
• Investigating POU2F3 in LUSC can reveal new therapeutic targets.

Purpose of the Study:

• To determine the clinical and biological significance of POU2F3 in LUSC.
• To assess the prognostic impact of POU2F3 expression in LUSC patients.
• To explore the transcriptomic and immune profiles associated with POU2F3 expression.

Main Methods:

• Analysis of RNA sequencing data from TCGA (n=190) and immunohistochemistry data from a surgical cohort (n=137).
• Survival analyses were performed to assess prognostic impact.
• Transcriptomic features, pathway enrichment, and immune profiles were evaluated using differential gene expression, GSEA, and CIBERSORTx.

Main Results:

• High POU2F3 expression predicted poor overall survival in the TCGA cohort (HR=2.06, P=0.039) but not in the IHC cohort (P=0.995).
• POU2F3-positive tumors showed enrichment for non-keratinizing and poorly differentiated subtypes.
• POU2F3 expression was associated with suppressed proliferation and immune pathways, and with p53/RB1 abnormalities.

Conclusions:

• POU2F3 identifies a transcriptionally distinct LUSC subtype with early-stage, keratinization-related features.
• The prognostic relevance of POU2F3 is context-dependent.
• Further validation in uniformly treated cohorts is required to confirm its prognostic value.