Lin Edwin, Lo Ying-Chun, Subbiah Vivek, Thawani Rajat, Desai Aakash
Mayo Clinic, Rochester, MN, USA.
Sarah Cannon Research Institute, Nashville, TN, USA.
Exp Hematol Oncol. 2025 Jul 11;14(1):96. doi: 10.1186/s40164-025-00685-w.
Antibody-drug conjugates (ADCs) represent a promising therapeutic strategy for non-small cell lung cancer (NSCLC), targeting tumor-specific antigens with precision. However, the molecular heterogeneity of NSCLC necessitates multiplex biomarker approaches to optimize ADC efficacy. This study utilized transcriptomics and proteomics to characterize NSCLC subtypes with distinct ADC target expression profiles. RNA-seq data from two independent cohorts (537 tumors, 59 controls; 338 tumors, 311 controls) identified clusters defined by overexpression of CEACAM5, MET, and TACSTD2, while normal lung tissue exhibited moderate TACSTD2 and FOLR1 expression. Chi-squared residual analysis revealed no significant associations with disease stage or driver mutations. Proteomic and transcriptomic data from 110 tumors and 101 controls demonstrated strong concordance. These findings highlight the potential of ADCs to target NSCLC subsets with distinct proteogenomic profiles, independent of disease stage or mutational status, underscoring their broad applicability in precision oncology.
抗体药物偶联物（ADCs）是一种很有前景的非小细胞肺癌（NSCLC）治疗策略，能够精准靶向肿瘤特异性抗原。然而，NSCLC的分子异质性需要采用多重生物标志物方法来优化ADC疗效。本研究利用转录组学和蛋白质组学来表征具有不同ADC靶标表达谱的NSCLC亚型。来自两个独立队列（537例肿瘤、59例对照；338例肿瘤、311例对照）的RNA测序数据确定了由CEACAM5、MET和TACSTD2过表达定义的聚类，而正常肺组织表现出中等水平的TACSTD2和FOLR1表达。卡方残差分析显示与疾病分期或驱动基因突变无显著关联。来自110例肿瘤和101例对照的蛋白质组学和转录组学数据显示出很强的一致性。这些发现突出了ADCs靶向具有不同蛋白质基因组谱的NSCLC亚群的潜力，而不受疾病分期或突变状态的影响，强调了它们在精准肿瘤学中的广泛适用性。
