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

Suguru Mitsui·Naoe Jimbo·Hiroyuki Ogawa·Shinya Tane·Daisuke Hokka·Yoshitaka Kitamura·Yoshimasa Maniwa·Tomoo Itoh
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Abstract

BACKGROUND: Lung squamous cell carcinoma (LUSC) lacks well-defined molecular targets. This study investigated the clinical and biological relevance of POU class 2 homeobox 3 (POU2F3), a tuft cell-associated transcription factor, in LUSC. METHODS: RNA sequencing data of patients with LUSC from The Cancer Genome Atlas (TCGA cohort, n&#xa0;=&#xa0;190) was analysed and compared to a cohort of surgically resected cases analyzed via immunohistochemistry (IHC cohort, n&#xa0;=&#xa0;137). Prognostic impact was assessed via survival analyses. Transcriptomic features, pathway enrichment, and immune profiles were evaluated via differentially expressed gene analysis, Gene Set Enrichment Analysis, and CIBERSORTx. RESULTS: High POU2F3 expression independently predicted poor overall survival in the TCGA cohort (HR&#xa0;=&#xa0;2.06, 95% CI: 1.04-4.08, P&#xa0;=&#xa0;0.039). In contrast, POU2F3 expression was not prognostic in the IHC cohort (P&#xa0;=&#xa0;0.995). Morphologically, POU2F3-positive tumours were enriched for non-keratinizing and poorly differentiated subtypes. Transcriptomic analysis showed suppression of proliferation and immune-related pathways (FDR&#xa0;<&#xa0;0.001), with suggestive enrichment of the TGF-&#x3b2; (FDR&#xa0;=&#xa0;0.143) and p53 (FDR&#xa0;=&#xa0;0.229) signaling pathways. On immune deconvolution, POU2F3-high tumours showed a nominal increase in activated dendritic cells, which did not withstand multiple testing correction. POU2F3 protein was detected in 12.4% of tumours and was significantly associated with p53 or RB1 abnormalities (single or double) (P&#xa0;=&#xa0;0.028). CONCLUSIONS: POU2F3 marks a transcriptionally distinct, early-stage subtype of LUSC with keratinization-related features. Its prognostic relevance appears context-dependent and requires prospective validation in uniformly treated cohorts.

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HumansPrognosisLung NeoplasmsCarcinoma, Squamous CellFemaleMaleImmunohistochemistryGene Expression ProfilingTranscriptomeBiomarkers, TumorMiddle AgedAgedGene Expression Regulation, NeoplasticPOU class 2 homeobox 3RNA sequencingimmunohistochemistrylung squamous cell carcinomaJournal Article

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Suguru Mitsui, Naoe Jimbo, Hiroyuki Ogawa, Shinya Tane, Daisuke Hokka, Yoshitaka Kitamura, Yoshimasa Maniwa, Tomoo Itoh. 2026-09-09. POU2F3 expression in lung squamous cell carcinoma: transcriptomic and immunohistochemical profiling with prognosis.. https://doi.org/10.1093/jjco%2Fhyag077

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