Biomedical subjects

Hiroyuki Ogawa

Publications and source records attributed to Hiroyuki Ogawa.

2 recordsLinked to original sources

PubMed2026

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

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 = 190) was analysed and compared to a cohort of surgically resected cases analyzed via immunohistochemistry (IHC cohort, n = 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 = 2.06, 95% CI: 1.04-4.08, P = 0.039). In contrast, POU2F3 expression was not prognostic in the IHC cohort (P = 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 < 0.001), with suggestive enrichment of the TGF-β (FDR = 0.143) and p53 (FDR = 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 = 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.

Humans↗

PubMed2026

Endobronchial Ultrasound-Guided Biopsy-Derived Lung Cancer Models: A Platform for Precision Therapy.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration is used for clinical diagnosis and staging in patients with lung cancer. Nevertheless, establishing patient-derived preclinical models using needle biopsy samples remains challenging. This study describes the establishment and utility of patient-derived organoid (PDO) from endobronchial ultrasound-guided (EBUS) specimens and EBUS patient-derived xenograft (PDX). METHODS: A total of 175 EBUS specimens were used to establish PDO and PDX. "Stable establishment" organoids with passage numbers of 10 or greater were used for genomic, transcriptome, and pathologic assessment. Drug sensitivity of EBUS organoids and PDX tumors were compared with those of the matched patient. Drug screening was performed using stably established organoid models. RESULTS: We successfully established a total of 20 EBUS organoids: six EBUS-PDOs and 14 EBUS-xenograft derived organoids. These stable cancer organoid models were validated for cancer cell enrichment and pathologic assessment. Pathologic findings, exome, and transcriptome analysis found a high correlation between EBUS organoids and parental samples. EBUS organoids and PDX indicated consistent drug response patterns with their corresponding patients. A drug screening conducted on an EBUS organoid led to the discovery of potent activity of trametinib to a rare MAP2K1 K57N mutation. CONCLUSIONS: EBUS-PDO and -xenograft‒derived organoids are good options to generate stable organoids in patients with advanced stage lung cancer. The models were consistent with the genetic and pathologic features of patient tumors, and the patient's responses to treatment, supporting their utility for novel therapeutic research.

Humans↗