Biological Difference between L858R and Exon 19 Deletion Contributes to Recurrence-Free Survival of Resected Non-Small Cell Lung Cancer
Biological Difference between L858R and Exon 19 Deletion Contributes to Recurrence-Free Survival of Resected Non-Small Cell Lung Cancer
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DOI：
10.1159/000526973
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发表时间：
2022-09
期刊：
影响因子：
3.5
通讯作者：
K. Masago;H. Kuroda;S. Fujita;E. Sasaki;Yusuke Takahashi;S. Shinohara;H. Matsushita
中科院分区：
文献类型：
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作者：
K. Masago;H. Kuroda;S. Fujita;E. Sasaki;Yusuke Takahashi;S. Shinohara;H. Matsushita
引言：经典EGFR突变的不同基因型之间的生物学特征差异尚未阐明。本研究旨在阐明L 858 R和19缺失在NSCLC中的临床和生物学差异。研究方法：我们分析了2006年1月至2021年9月期间在日本名古屋爱知癌症中心医院进行根治性切除并随后复发的191例携带EGFR驱动突变（L 858 R或19缺失）的手术切除NSCLC连续病例队列。我们还对61例手术切除的携带EGFR驱动突变（L 858 R或19缺失）的NSCLC标本进行了RNA测序分析。结果如下：在I期疾病患者中，EGFR突变类型之间的中位至复发时间无统计学显著性差异;然而，在II期和III期疾病患者中，与19缺失患者相比，L 858 R基因型患者的中位至复发时间往往较短（对数秩检验，分别为p = 0.47和0.46）。与19个缺失肿瘤相比，L 858 R肿瘤具有更高的细胞学恶性度（例如，有丝分裂能力），并显示出更强的免疫原性。结论：L 858 R和19缺失肿瘤的复发时间可能略有差异。他们认为，即使在作为同一疾病类别治疗的EGFR驱动肿瘤中，肿瘤的生物学特征也是不同的，这可能为术后治疗和复发时的治疗留下创新空间。
Introduction: The differences in biological characteristics among different genotypes of classical EGFR mutations have not been clarified. This study aimed to clarify the clinical and biological differences between L858R and 19 deletion in NSCLC. Methods: We analyzed a cohort of 191 consecutive cases of surgically resected NSCLC harboring EGFR driver mutations (L858R or 19 deletion) in which curative resection was performed in Aichi Cancer Center Hospital, Nagoya, Japan, from January 2006 to September 2021 and in which recurrence subsequently developed. We also subjected 61 surgically resected NSCLC specimens harboring EGFR driver mutations (L858R or 19 deletion) to an RNA sequencing analysis. Results: In patients with stage I disease, the median time to recurrence did not differ to a statistically significant extent between the types of EGFR mutations; however, among those with stage II and III disease, the median time to recurrence in patients with the L858R genotype tended to be shorter in comparison to those with 19 deletion (log-rank test, p = 0.47 and 0.46, respectively). In comparison to 19 deletion tumors, L858R tumors had higher cytological malignancy (e.g., mitotic ability) and showed stronger immunogenicity. Conclusion: L858R and 19 deletion tumors are likely to have a slight difference in the time to recurrence. They suggest that even in EGFR driver tumors, which are treated as the same disease category, the biological characteristics of the tumors are different, which may leave room for innovations in postoperative treatment and treatment at recurrence.