1 Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
2 Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Int J Biol Markers. 2019 Mar;34(1):90-97. doi: 10.1177/1724600818803104. Epub 2019 Mar 10.
PURPOSE/OBJECTIVES: We aimed to assess the predictive value of a lung cancer gene panel for the development of brain metastases.
MATERIALS/METHODS: Between 2011 and 2015, 102 patients with lung cancer were prospectively enrolled in a clinical trial in which a diagnostic fine-needle aspirate was obtained. Gene expression was conducted on all samples that rendered a diagnosis of non-small cell lung cancer (NSCLC). Subsequent retrospective analysis of brain metastases-related outcomes was performed by reviewing patient electronic medical records. A competing risk multivariable regression was performed to estimate the adjusted hazard ratio for the development of brain metastases and non-brain metastases from NSCLC.
A total of 49 of 102 patients had died by the last follow-up. Median time of follow-up was 13 months (range 0.23-67 months). A total of 17 patients developed brain metastases. Median survival time after diagnosis of brain metastases was 3.58 months (95% confidence interval (CI) 2.17, not available). A total of 30 patients developed metastases without any evidence of brain metastases until the time of death or last follow-up. Competing risk analysis identified three genes that were downregulated differentially in the patients with brain metastases versus non-brain metastatic disease: CD37 (0.017), cystatin A (0.022), and IL-23A (0.027). Other factors associated with brain metastases include: stage T ( P ⩽ 8.3e) and stage N ( P= 6.8e).
We have identified three genes, CD37, cystatin A, and IL-23A, for which downregulation of gene expression was associated with a greater propensity for developing brain metastases. Validation of these biomarkers could have implications on surveillance patterns in patients with brain metastases from NSCLC.
评估肺癌基因panel 对脑转移发生的预测价值。
材料/方法：2011 年至 2015 年，前瞻性纳入了 102 例肺癌患者，对所有诊断为非小细胞肺癌（NSCLC）的样本进行基因表达分析。回顾性分析了患者的电子病历，以评估脑转移相关结局。采用竞争风险多变量回归估计 NSCLC 脑转移和非脑转移的调整后危险比。
截至最后一次随访时，102 例患者中共有 49 例死亡。中位随访时间为 13 个月（范围 0.23-67 个月）。共 17 例患者发生脑转移。脑转移诊断后中位生存时间为 3.58 个月（95%置信区间 2.17，无法计算）。共有 30 例患者在死亡或最后一次随访时出现了没有脑转移证据的转移。竞争风险分析确定了在发生脑转移与非脑转移疾病的患者之间存在差异下调的三个基因：CD37（0.017）、胱抑素 A（0.022）和 IL-23A（0.027）。与脑转移相关的其他因素包括：T 分期（ P ⩽ 8.3e）和 N 分期（ P= 6.8e）。
我们发现了三个基因，CD37、胱抑素 A 和 IL-23A，其基因表达下调与发生脑转移的倾向性增加相关。这些生物标志物的验证可能对非小细胞肺癌脑转移患者的监测模式产生影响。
