■发现驱动基因,如EGFR,KRAS,ALK,极大地改变了携带这些癌基因的患者的治疗模式。然而,传播到中枢神经系统(CNS)是一种严重的并发症。此外,中枢神经系统的特殊解剖结构使得很难从脑转移瘤(BM)中获得组织标本以生成基因图谱,因此,非小细胞肺癌(NSCLC)和BM(NSCLC-BM)患者生存的潜在预测标志物尚不清楚.
■来自2019年6月至2021年5月在广东省三九脑科医院诊断为NSCLC-BM的28例患者的数据(广州,中国),被审查了。168个癌症相关基因小组的靶向下一代测序(NGS)可用于所有患者手术切除的脑组织。此外,分析了分子特征和总生存期(OS),以确定潜在的预测标志物.
■在NSCLC-BM患者中,NGS显示TP53是最常见的突变(61%),检出率为39%,密切通过EGFR扩增。此外,CDKN2A,MYC,LRP1B,经常观察到RNF43(18%)。TP53突变组的中位OS明显短于野生型组(14个月与未定义月相比,p=0.014)。在EGFR扩增的遗传改变中也发现了类似的结果,表明EGFR扩增与OS恶化相关(14与24个月,p=0.039)。有趣的是,NGS显示基因改变,如TP53,EGFR扩增,和CDKN2A,倾向于共存,这样的共同改变小组表明临床结局更差(中位OS,5个月)。此外,阴性生存基因的检出率,包括TP53或EGFR扩增,在肿瘤组织中比在血浆样本中高得多,表明匹配的PLA样品的预测值有限。
■基因特征,如TP53或EGFR扩增,在诊断为NSCLC-BM的患者中与较差的生存率相关。这些有价值的发现可能为特定患者组的预后评估提供新策略。
UNASSIGNED: The discovery of driver genes such as EGFR, KRAS, and ALK, has dramatically shifted treatment patterns in patients harboring these oncogenes. However, dissemination into the central nervous system (CNS) is a severe complication. In addition, the particular anatomical structure of the CNS has made it difficult to obtain tissue specimens from brain metastases (BM) to generate a gene map, as such, potential predictive markers for survival in patients with non-small cell lung cancer (NSCLC) and BM (NSCLC-BM) remain unclear.
UNASSIGNED: Data from 28 patients diagnosed with NSCLC-BM between June 2019 and May 2021 at Guangdong Sanjiu Brain Hospital (Guangzhou, China), were reviewed. Targeted next-generation sequencing (NGS) of a 168 cancer-related gene panel was available for surgically resected brain tissues from all patients. In addition, molecular characteristics and overall survival (OS) were analyzed to determine potential predictive markers.
UNASSIGNED: Among patients with NSCLC-BM, NGS revealed that
TP53 was the most frequent mutation (61 %), with a detection rate of 39 %, closely by EGFR amplification. Additionally, CDKN2A, MYC, LRP1B, and RNF43 were frequently observed (18 %). The median OS was significantly shorter in the
TP53 mutation group than in the wildtype group (14 versus undefined months, p = 0.014). Similar results were also found in the genetic alteration of EGFR amplification, suggesting that EGFR amplification was associated with worse OS (14 vs. 24 months, p = 0.039). Interestingly, NGS revealed that gene alternations such as
TP53, EGFR amplification, and CDKN2A, tended to coexist and such a co-alteration panel indicated worse clinical outcomes (median OS, 5 months). In addition, the detection rate of negative survival genes, including
TP53 or EGFR amplification, was much higher in tumor tissues than in plasma samples, indicating the limited predictive value of matched PLA samples.
UNASSIGNED: Gene signatures, such as
TP53 or EGFR amplification, were associated with worse survival in patients diagnosed with NSCLC-BM. These valuable findings may shed light on new strategies for the prognostic assessment of specific patient groups.