Abstract：
BACKGROUND: To assess the genetic characteristics of central nervous system (CNS) metastases from non-small-cell lung cancer (NSCLC), we gathered the genetic profiles of brain metastases (BM) and leptomeningeal metastases (LM). Our objective was to identify genetic factors contributing to poorer overall survival (OS) in NSCLC patients with LM.
METHODS: This study included 25 consecutive patients with BM and 52 patients with LM from Guangdong Sanjiu Brain Hospital. All participants underwent 168-target panel sequencing.
RESULTS: Among the 25 patients with BM, TP53 was the most frequently mutated gene (44%), followed by driver genes such as EGFR and BRAF (40% and 20%, respectively). In patients with BM, EGFR_amp and CDK4 were also frequently mutated, with rates of 20% and 16%, respectively. The genetic landscape of patients with LM differed, with the top mutated genes being EGFR, TP53, EGFR_amp, CDKN2A, CCNE1, CDK4, PMS2, and PIK3CA, with mutation rates of 77%, 69%, 31%, 29%, 13%, 13%, 13%, and 12%, respectively. In our study, patients with LM exhibited significantly worse OS compared to those with BM (p = 0.029). The mutation rates of TP53, EGFR_amp, and CDKN2A varied between patients with LM and those with BM, at 69.23% vs. 44%, 30.77% vs. 20%, and 28.85% vs. 12%, respectively. Further exploration revealed that patients with BM with TP53 mutations had a shorter OS than patients without TP53 mutations (p = 0.014). Similarly, patients with LM and TP53 mutations presented with worse OS than those without TP53 mutations (p = 0.0067). LM patients with CDKN2A deletions had worse OS than those without CDKN2A deletions (p = 0.037). Additionally, patients with EGFR_amp had a shorter OS than those without EGFR_amp (p = 0.044).
CONCLUSIONS: Patients with LM exhibited significantly worse OS than those with BM. Gene signatures, such as TP53, EGFR_amp, and CDKN2A, may account for shorter outcomes in patients with LM.
METHODS: This study included 25 consecutive patients with BM and 52 patients with LM from Guangdong Sanjiu Brain Hospital. All participants underwent 168-target panel sequencing.
RESULTS: Among the 25 patients with BM, TP53 was the most frequently mutated gene (44%), followed by driver genes such as EGFR and BRAF (40% and 20%, respectively). In patients with BM, EGFR_amp and CDK4 were also frequently mutated, with rates of 20% and 16%, respectively. The genetic landscape of patients with LM differed, with the top mutated genes being EGFR, TP53, EGFR_amp, CDKN2A, CCNE1, CDK4, PMS2, and PIK3CA, with mutation rates of 77%, 69%, 31%, 29%, 13%, 13%, 13%, and 12%, respectively. In our study, patients with LM exhibited significantly worse OS compared to those with BM (p = 0.029). The mutation rates of TP53, EGFR_amp, and CDKN2A varied between patients with LM and those with BM, at 69.23% vs. 44%, 30.77% vs. 20%, and 28.85% vs. 12%, respectively. Further exploration revealed that patients with BM with TP53 mutations had a shorter OS than patients without TP53 mutations (p = 0.014). Similarly, patients with LM and TP53 mutations presented with worse OS than those without TP53 mutations (p = 0.0067). LM patients with CDKN2A deletions had worse OS than those without CDKN2A deletions (p = 0.037). Additionally, patients with EGFR_amp had a shorter OS than those without EGFR_amp (p = 0.044).
CONCLUSIONS: Patients with LM exhibited significantly worse OS than those with BM. Gene signatures, such as TP53, EGFR_amp, and CDKN2A, may account for shorter outcomes in patients with LM.
摘要：
背景：为了评估非小细胞肺癌（NSCLC）中枢神经系统（CNS）转移的遗传特征，我们收集了脑转移瘤(BM)和软脑膜转移瘤(LM)的基因图谱.我们的目标是确定导致LMNSCLC患者总生存期（OS）较差的遗传因素。
方法：本研究纳入广东省三九脑科医院连续25例BM患者和52例LM患者。所有参与者都进行了168个目标组测序。
结果：在25例BM患者中，TP53是最常见的突变基因（44％），其次是EGFR和BRAF等驱动基因(40%和20%，分别)。在BM患者中，EGFR_amp和CDK4也经常发生突变，20%和16%的比率，分别。LM患者的遗传景观不同，最重要的突变基因是EGFR，TP53,EGFR_amp,CDKN2A,CCNE1、CDK4、PMS2和PIK3CA，突变率为77%,69%,31%,29%,13%,13%,13%,12%,分别。在我们的研究中,与BM患者相比,LM患者的OS显著更差(p=0.029).TP53、EGFR_amp、CDKN2A在LM患者和BM患者之间有所不同，在69.23%与44%,30.77%与20%,和28.85%与12%,分别。进一步的研究发现，具有TP53突变的BM患者的OS比没有TP53突变的患者短（p=0.014）。同样，有LM和TP53突变的患者的OS比没有TP53突变的患者差(p=0.0067).有CDKN2A缺失的LM患者的OS比没有CDKN2A缺失的患者差(p=0.037)。此外,EGFR_amp患者的OS比无EGFR_amp患者短(p=0.044).
结论：LM患者的OS明显低于BM患者。基因特征,如TP53，EGFR_amp，和CDKN2A，可能是LM患者预后较短的原因。
方法：本研究纳入广东省三九脑科医院连续25例BM患者和52例LM患者。所有参与者都进行了168个目标组测序。
结果：在25例BM患者中，TP53是最常见的突变基因（44％），其次是EGFR和BRAF等驱动基因(40%和20%，分别)。在BM患者中，EGFR_amp和CDK4也经常发生突变，20%和16%的比率，分别。LM患者的遗传景观不同，最重要的突变基因是EGFR，TP53,EGFR_amp,CDKN2A,CCNE1、CDK4、PMS2和PIK3CA，突变率为77%,69%,31%,29%,13%,13%,13%,12%,分别。在我们的研究中,与BM患者相比,LM患者的OS显著更差(p=0.029).TP53、EGFR_amp、CDKN2A在LM患者和BM患者之间有所不同，在69.23%与44%,30.77%与20%,和28.85%与12%,分别。进一步的研究发现，具有TP53突变的BM患者的OS比没有TP53突变的患者短（p=0.014）。同样，有LM和TP53突变的患者的OS比没有TP53突变的患者差(p=0.0067).有CDKN2A缺失的LM患者的OS比没有CDKN2A缺失的患者差(p=0.037)。此外,EGFR_amp患者的OS比无EGFR_amp患者短(p=0.044).
结论：LM患者的OS明显低于BM患者。基因特征,如TP53，EGFR_amp，和CDKN2A，可能是LM患者预后较短的原因。
