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Updated: Sep 8, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Translational Analysis of NSD3 Gene Amplification in Lung Squamous Cell Carcinoma: Clinical and Prognostic Insights
Shugo Takahashi1, Tetsuro Taki2, Nobuyuki Nakamura3
1Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan.
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.
