Genomic Signature for Initial Brain Metastasis Velocity (iBMV) in Non-Small-Cell Lung Cancer Patients: The Elusive Biomarker to Predict the Development of Brain Metastases?

IF 4.5 2区 医学 Q1 ONCOLOGY
Cancers Pub Date : 2025-03-15 DOI:10.3390/cancers17060991
Sarah E Glynn, Claire M Lanier, Ariel R Choi, Ralph D'Agostino, Michael Farris, Mohammed Abdulhaleem, Yuezhu Wang, Margaret Smith, Jimmy Ruiz, Thomas Lycan, William Jeffrey Petty, Christina K Cramer, Stephen B Tatter, Adrian W Laxton, Jaclyn J White, Jing Su, Christopher T Whitlow, David R Soto-Pantoja, Fei Xing, Yuming Jiang, Michael Chan, Corbin A Helis
{"title":"Genomic Signature for Initial Brain Metastasis Velocity (iBMV) in Non-Small-Cell Lung Cancer Patients: The Elusive Biomarker to Predict the Development of Brain Metastases?","authors":"Sarah E Glynn, Claire M Lanier, Ariel R Choi, Ralph D'Agostino, Michael Farris, Mohammed Abdulhaleem, Yuezhu Wang, Margaret Smith, Jimmy Ruiz, Thomas Lycan, William Jeffrey Petty, Christina K Cramer, Stephen B Tatter, Adrian W Laxton, Jaclyn J White, Jing Su, Christopher T Whitlow, David R Soto-Pantoja, Fei Xing, Yuming Jiang, Michael Chan, Corbin A Helis","doi":"10.3390/cancers17060991","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background/Objectives</b>: No prior studies have attempted to identify a biomarker for initial brain metastasis velocity (iBMV), with limited studies attempting to correlate genomic data with the development of brain metastases. <b>Methods</b>: Patients with non-small-cell lung cancer (NSCLC) who underwent next-generation sequencing (NGS) were identified in our departmental database. iBMV was calculated by dividing the number of BMs by the interval of time between primary cancer and BM diagnosis. Two-sample <i>t</i>-testing was used to identify mutations statistically associated with iBMV (<i>p</i> < 0.1). A value of +1 was assigned to each mutation with a positive association (\"deleterious genes\"), and a value of -1 to each with an inverse association (\"protective genes\"). The sum of these values was calculated to define iBMV risk scores of -1, 0 and 1. Pearson correlation test was used to determine the association between iBMV risk score and calculated iBMV, and a competing risk analysis assessed for death as a competing risk to the development of BMs. <b>Results</b>: A total of 312 patients were included in the analysis, 218 of whom (70%) developed brain metastases. \"Deleterious genes\" included ARID1A, BRAF, CDK4, GNAQ, MLH1, MSH6, PALB2, RAD51D, RB1 and TSC1; \"protective genes\" included ARAF, IDH1, MYC, and PTPN11. iBMV risk scores of 1, 0 and -1, predicted an 88%, 61% and 65% likelihood of developing a BM (<i>p</i> < 0.01). A competing risk analysis found a significant association between iBMV risk scores of 1 vs. 0 and 1 vs. -1, and the likelihood of developing a BM using death as a competing risk. Overall survival (OS) at 1 and 2 years for patients with iBMV risk scores of 1, 0 and -1 was 72% vs. 84% vs. 85% and 46% vs. 69% vs. 70% (<i>p</i> < 0.02). <b>Conclusions</b>: Development of a genomic signature for iBMV via non-invasive liquid biopsy appears feasible in NSCLC patients. Patients with a positive iBMV risk score were more likely to develop brain metastases. Validation of this signature could lead to a biomarker with the potential to guide treatment recommendations and surveillance schedules.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941343/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancers","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/cancers17060991","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background/Objectives: No prior studies have attempted to identify a biomarker for initial brain metastasis velocity (iBMV), with limited studies attempting to correlate genomic data with the development of brain metastases. Methods: Patients with non-small-cell lung cancer (NSCLC) who underwent next-generation sequencing (NGS) were identified in our departmental database. iBMV was calculated by dividing the number of BMs by the interval of time between primary cancer and BM diagnosis. Two-sample t-testing was used to identify mutations statistically associated with iBMV (p < 0.1). A value of +1 was assigned to each mutation with a positive association ("deleterious genes"), and a value of -1 to each with an inverse association ("protective genes"). The sum of these values was calculated to define iBMV risk scores of -1, 0 and 1. Pearson correlation test was used to determine the association between iBMV risk score and calculated iBMV, and a competing risk analysis assessed for death as a competing risk to the development of BMs. Results: A total of 312 patients were included in the analysis, 218 of whom (70%) developed brain metastases. "Deleterious genes" included ARID1A, BRAF, CDK4, GNAQ, MLH1, MSH6, PALB2, RAD51D, RB1 and TSC1; "protective genes" included ARAF, IDH1, MYC, and PTPN11. iBMV risk scores of 1, 0 and -1, predicted an 88%, 61% and 65% likelihood of developing a BM (p < 0.01). A competing risk analysis found a significant association between iBMV risk scores of 1 vs. 0 and 1 vs. -1, and the likelihood of developing a BM using death as a competing risk. Overall survival (OS) at 1 and 2 years for patients with iBMV risk scores of 1, 0 and -1 was 72% vs. 84% vs. 85% and 46% vs. 69% vs. 70% (p < 0.02). Conclusions: Development of a genomic signature for iBMV via non-invasive liquid biopsy appears feasible in NSCLC patients. Patients with a positive iBMV risk score were more likely to develop brain metastases. Validation of this signature could lead to a biomarker with the potential to guide treatment recommendations and surveillance schedules.

背景/目标:之前没有研究试图确定初始脑转移速度(iBMV)的生物标志物,尝试将基因组数据与脑转移发展相关联的研究也很有限。研究方法iBMV 的计算方法是将脑转移数量除以原发性癌症与脑转移诊断之间的时间间隔。采用双样本 t 检验确定与 iBMV 有统计学关联的突变(p < 0.1)。每个与iBMV呈正相关的突变("有害基因")的值为+1,每个与iBMV呈反相关的突变("保护基因")的值为-1。使用皮尔逊相关性检验确定 iBMV 风险评分与计算出的 iBMV 之间的关联,并进行竞争风险分析,评估死亡作为 BMs 发病的竞争风险。结果共有 312 例患者纳入分析,其中 218 例(70%)发生了脑转移。"致病基因 "包括 ARID1A、BRAF、CDK4、GNAQ、MLH1、MSH6、PALB2、RAD51D、RB1 和 TSC1;"保护基因 "包括 ARAF、IDH1、MYC 和 PTPN11。iBMV 风险评分为 1、0 和 -1 时,预测发生脑转移的可能性分别为 88%、61% 和 65%(p < 0.01)。竞争风险分析发现,以死亡作为竞争风险,iBMV 风险评分为 1 与 0、1 与 -1 之间与罹患骨髓瘤的可能性存在显著关联。iBMV风险评分为1、0和-1的患者1年和2年的总生存率(OS)分别为72% vs. 84% vs. 85%和46% vs. 69% vs. 70%(P < 0.02)。结论通过非侵入性液体活检为NSCLC患者开发iBMV基因组特征似乎是可行的。iBMV风险评分呈阳性的患者更有可能发生脑转移。对这一特征的验证可能会产生一种生物标记物,并有可能指导治疗建议和监测计划。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Cancers
Cancers Medicine-Oncology
CiteScore
8.00
自引率
9.60%
发文量
5371
审稿时长
18.07 days
期刊介绍: Cancers (ISSN 2072-6694) is an international, peer-reviewed open access journal on oncology. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信