晚期非小细胞肺癌中间质上皮细胞转化因子扩增的分子特征及其预后价值

Molecular characteristics and prognostic value of mesenchymal-epithelial transition factor amplification in advanced non-small cell lung cancer

    摘要
  • 摘要:
    目的 分析晚期非小细胞肺癌中间质上皮细胞转化因子（mesenchymal-epithelial transition factor，MET）扩增的分子特征及其预后价值。
    方法 收集2018年1月至2024年12月中国医学科学院肿瘤医院进行治疗的48例晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）病例的组织样本，应用下一代测序技术检测样本的MET扩增情况及其他基因变异情况；应用C-MET VentanaSP44抗体检测样本中MET过表达情况；收集临床病理资料进行回顾性分析。
    结果 本研究共纳入48例NSCLC样本，其中MET低倍扩增18例，扩增30例。在所有病例中，66.7%（32/48）表现为MET基因扩增与MET蛋白过表达共存。进一步分析显示，扩增组有86.7%（26/30）的病例同时存在MET蛋白过表达，低倍扩增组33.3%(6/18)的病例同时存在MET蛋白过表达。统计分析表明，MET扩增结果与MET过表达结果（C-MET VentanaSP44）之间无显著相关性；低倍扩增组和扩增组在性别、吸烟、原发灶/转移灶、脑转移、年龄、程序性死亡受体-配体1（programmed death-ligand 1，PD-L1）表达、表皮生长因子受体（epidermal growth factor receptor，EGFR）状态、原发/继发扩增、表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitor，EGFR TKI）治疗史和MET酪氨酸激酶抑制剂(MET tyrosine kinase inhibitor，MET TKI)治疗史等临床病理特征方面无明显差异；生存分析显示，全组患者的中位总生存期（median overall survival，mOS）为23.2个月，且扩增组与低倍扩增组之间的OS无显著性差异；MET TKI治疗组的中位无进展生存期（median progression-free survival，mPFS）为5.3个月，其中Ⅲ代EGFR TKI与MET TKI联合治疗组的中位PFS为5.6个月，进一步分析显示，在MET TKI治疗队列中，扩增组与低倍扩增组的OS和PFS无统计学差异（P>0.05）。
    结论 MET基因扩增结果与MET蛋白过表达结果（C-MET VentanaSP44）之间无显著相关性；当MET基因扩增拷贝数（copy number，CN）≥5时，预示着其与MET蛋白过表达共存的可能性更高；MET基因低倍扩增组与扩增组之间总生存期无显著性差异。

     

    Abstract:
    Objective To analyze the molecular characteristics and prognostic value of mesenchymal-epithelial transition factor (MET)-amplified advanced non-small-cell lung cancer (NSCLC).
    Methods Tissue samples were collected from 48 patients with advanced NSCLC and MET amplification treated at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2018 and December 2024. Next-generation sequencing was used to detect MET amplification and other genetic variations. MET overexpression was assessed using the C-MET VentanaSP44 antibody. Clinicopathological data were collected in this retrospective study.
    Results Among 48 MET-amplified advanced NSCLC samples, low- and high-level amplification was observed in 18 and 30 samples, respectively. Among these, 66.7% (32/48) showed the co-occurrence of MET gene amplification and protein overexpression. The amplification and low-level amplification groups demonstrated co-occurrence in 86.7% (26/30) and 33.3% (6/18) of the cases, respectively. No significant differences were observed between the low- and high-level amplification groups in terms of sex, smoking history, primary or secondary sites, brain metastasis, age, programmed death-ligand 1 (PD-L1) expression, epidermal growth factor receptor (EGFR) status, primary or secondary amplification, history of EGFR tyrosine kinase inhibitor (EGFR TKI) therapy, or history of MET TKI therapy. After follow-up and statistical analyses, the median overall survival (mOS) of the entire cohort was 23.2 months, with no significant difference in OS between the high- and low-level amplification groups. The median progression-free survival (mPFS) for the MET TKI treatment group was 5.3 months, whereas the median PFS for the combination therapy group (third-generation EGFR TKI and MET TKI) was 5.6 months. OS and PFS showed no significant differences between the high- and low-level amplification groups among MET TKI-treated cases.
    Conclusions No significant correlation was observed between MET amplification and MET overexpression (C-MET VentanaSP44). An MET gene copy number (CN) ≥5 predicted a higher probability of concurrent MET protein overexpression. No significant differences in OS and PFS were observed between the high- and low-level amplification groups among MET TKI-treated cases.

     

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