Different genetic profiles contribute to worse overall survival in patients with leptomeningeal metastases of non-small-cell lung cancer.

IF 2.8 3区医学 Q2 ONCOLOGY Clinical & Translational Oncology Pub Date : 2024-12-01 Epub Date: 2024-05-25 DOI:10.1007/s12094-024-03507-3

Xusheng Tang, Xiaojuan Hu, Lin Yuan, Hainan Yang, Yunfen Luo, Da Liu, Qingjun Hu, Changguo Shan, Tao Lin, Linbo Cai, Zhaoming Zhou, Xin Jin, Ming Lei, Weiping Hong

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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.

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不同的遗传特征导致非小细胞肺癌脑膜转移患者的总生存率降低。

背景：为了评估非小细胞肺癌（NSCLC）中枢神经系统（CNS）转移灶的遗传特征，我们收集了脑转移灶（BM）和钩端膜转移灶（LM）的遗传特征。我们的目的是找出导致NSCLC脑转移瘤患者总生存期（OS）较差的遗传因素：本研究纳入了广东三九脑科医院的25例连续性BM患者和52例LM患者。所有参与者均接受了168个靶点的面板测序：结果：在25名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（分别为40%和20%）。在骨髓瘤患者中，表皮生长因子受体_amp和CDK4也经常发生突变，突变率分别为20%和16%。LM患者的基因情况有所不同，突变率最高的基因是表皮生长因子受体、TP53、表皮生长因子受体_amp、CDKN2A、CCNE1、CDK4、PMS2和PIK3CA，突变率分别为77%、69%、31%、29%、13%、13%、13%和12%。在我们的研究中，LM 患者的 OS 明显低于 BM 患者（P = 0.029）。LM患者和BM患者的TP53、EGFR_amp和CDKN2A突变率不同，分别为69.23%对44%、30.77%对20%和28.85%对12%。进一步研究发现，TP53突变的BM患者的OS短于无TP53突变的患者（P = 0.014）。同样，LM和TP53突变患者的OS也比没有TP53突变的患者差（p = 0.0067）。CDKN2A缺失的LM患者的OS比没有CDKN2A缺失的患者更差（p = 0.037）。此外，EGFR_amp患者的OS短于无EGFR_amp的患者（p = 0.044）：结论：LM 患者的 OS 明显差于 BM 患者。TP53、表皮生长因子受体_amp和CDKN2A等基因特征可能是导致LM患者预后较短的原因。

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来源期刊

Clinical & Translational Oncology 医学-肿瘤学

CiteScore

6.20

自引率

2.90%

发文量

240

审稿时长

1 months

期刊介绍： Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.