クボタ　ショウコ   KUBOTA Shouko   久保田　晶子    所属   医学部 医学科（附属足立医療センター）    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Translational Analysis of NSD3 Gene Amplification in Lung Squamous Cell Carcinoma: Clinical and Prognostic Insights From Histopathologic Analysis of Patient Samples.
掲載誌名	正式名：Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 略　 称：J Thorac Oncol ISSNコード：15561380/15560864
掲載区分	国外
巻・号・頁	21(1),pp.135-149
著者・共著者	Shugo Takahashi, Tetsuro Taki, Nobuyuki Nakamura, Ayako Ura, Shoko Kubota, Tomohiro Miyoshi, Kenta Tane, Yuki Matsumura, Joji Samejima, Keiju Aokage, Masashi Wakabayashi, Yukiko Sasahara, Michiko Nagamine, Motohiro Kojima, Shingo Sakashita, Naoya Sakamoto, Takuo Hayashi, Kazuya Takamochi, Kenji Suzuki, Masahiro Tsuboi, Genichiro Ishii
発行年月	2026/01
概要	INTRODUCTION:Nuclear receptor-binding SET domain 3 (NSD3) has been implicated as a driver of lung squamous cell carcinoma (LUSC) in preclinical studies. However, its clinicopathologic characteristics and prognostic significance remain unclear. To address this, we performed a histopathologic analysis of patient tissues.METHODS:The NSD3 gene copy number was evaluated using fluorescence in situ hybridization in multiple cohorts of surgically resected LUSC cases, categorized into the amplification (Amp) or diploidy (Diploidy) groups. Clinicopathologic characteristics were compared, and artificial intelligence-based histopathologic image analysis evaluated the associations between NSD3 amplification, its protein expression, and cancer cell proliferation activity.RESULTS:In the original cohort, NSD3 amplification was detected in 106 patients (39.6%). NSD3 protein expression was positively correlated with the NSD3 gene copy number (r = 0.528, p < 0.001). The Amp group exhibited higher mitotic counts (18 versus 13, p = 0.004) and Ki-67 index (18.5% versus 13.6%, p = 0.009) than the Diploidy group. The Amp group had shorter overall survival than the Diploidy group (110.6 versus 125.3 mo, p = 0.030), and multivariable analysis identified NSD3 amplification as an independent poor prognostic factor (hazard ratio = 1.59, p = 0.049). Furthermore, validation cohort analyses demonstrated consistent associations of NSD3 gene amplification with protein expression and cell proliferation, with comparable hazard ratios in prognostic evaluation.CONCLUSIONS:Our study highlights the clinical relevance of NSD3 amplification in LUSC through analyses of patient tissues. These findings emphasize the potential of NSD3 as a prognostic biomarker and therapeutic target, bridging the gap between preclinical research and clinical application.
DOI	10.1016/j.jtho.2025.08.022
PMID	40912657