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在小细胞肺癌和转化非小细胞肺癌中SEZ6表达和血统可塑性

Jennifer A Marks¹, Kieran Sweeney², Andrew Elliott²

¹Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston 02215 MA, USA.

Lung cancer (Amsterdam, Netherlands)

|January 14, 2026

概括

与相关的同类素6 (SEZ6) 在小细胞肺癌 (SCLC) 和转化非小细胞肺癌 (NSCLC) 中升高,这表明它是治疗点. 较高的SEZ6表达与这些侵袭性神经内分泌瘤的生存时间较短有关.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
癌症治疗方法癌症治疗方法

背景情况:

小细胞肺癌 (SCLC) 和肺外神经内分泌 (NE) 瘤是具有有限治疗选择的侵袭性癌症.
与发作相关的同源6 (SEZ6) 是一个潜在的治疗标,但其在这些瘤中的表达还不清楚.
非小细胞肺癌 (NSCLC) 的血统可塑性可能导致SCLC转变,从而导致治疗耐药性.

研究的目的:

描述SEZ6在各种神经内分泌 (NE) 瘤中的表达.
调查SEZ6表达非小细胞肺癌 (NSCLC) 已转化为小细胞肺癌 (SCLC) 的病例.
探索SEZ6表达和NE血统标记 (ASCL1,NEUROD1,POU2F3) 和患者存活率之间的相关性.

主要方法:

对1318个SCLC,2218个NE和NSCLC样本进行了RNA测序.
样品根据SEZ6RNA表达四分位数进行分层,并根据ASCL1,NEUROD1和POU2F3表达分类.
总体生存数据使用现实世界保险索赔数据和日志等级测试来分析.

主要成果:

与NE瘤 (20.8 TPM) 和NSCLC (1.34 TPM) 相比,SCLC (39.7 TPM) 的中位数SEZ6表达显著更高.
在NE瘤中,SEZ6的表达有所不同,在前列腺中最高 (52.0 TPM),在上腺瘤中最低 (1.2 TPM).
从NSCLC转化为SCLC的样本显示SEZ6表达的显著增加 (中位数:86.2 TPM与2.4 TPM).

结论:

在SCLC和转化NSCLC中,SEZ6显著过度表达,将其定位为有前途的治疗标.
SEZ6表达与NE血统标记相关,并与较短的存活期有关,这表明它在风险分层中的有用性.
针对SEZ6,可能通过抗体-药物合物 (ADCs),可以为侵袭性NE恶性瘤和耐治疗的转变瘤提供新的治疗策略.

关键词:

血统的可塑性血统的可塑性在NSCLCLC中,我们可以看到.神经内分泌瘤的神经内分泌瘤在SCLC中,SCLC是最重要的.这里是SEZ6 SEZ6.

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