Li Ji, Jing Wang, Jia Wenxiao, Zhai Xiaoyang, Zhu Hui, Yu Jinming
Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Front Oncol. 2021 May 17;11:603271. doi: 10.3389/fonc.2021.603271. eCollection 2021.
The purpose of this study was to identify aberrant long non-coding RNAs (lncRNAs) and explore the predictive value of lncRNA expression patterns on the risk of brain metastases (BMs) in patients with limited-stage small-cell lung cancer (SCLC). We executed an array of lncRNA and mRNA chip assays to examine the expression in peripheral blood mononuclear cells obtained from SCLC patients with BMs and compared the expression patterns against those from patients without BMs to identify lncRNAs associated with BMs. Validation was performed against clinical data to further confirm the relationship between lncRNAs and BM. Kaplan-Meier analysis was applied to estimate the cumulative incidence of BMs, and differences between the groups were analyzed using the log-rank test. The expression of 67 lncRNAs (27 upregulated and 40 downregulated) and 47 mRNAs (20 upregulated and 27 downregulated) was significantly different between the BM and non-BM groups (fold change ≥ 2.0, -value ≤ 0.05), based on the lncRNA and mRNA chip assays. Four lncRNAs were verified by quantitative real-time polymerase chain reaction (qRT-PCR) to confirm the accuracy of the microarray data, and the results of 11 patient pairs (11 patients with BM and 11 patients without BM) revealed that low LncRNA XR_429159.1 expression was a high-risk factor for BM. Further clinical data showed that the incidence of BM among 25 patients with low-level LncRNA XR_429159.1 expression was 31% at 1 year, compared with 14.3% among the 18 patients with high-level LncRNA XR_429159.1 expression ( = 0.035). Our present study identified the low-level expression of lncRNA XR_429159.1 as a high-risk factor among BM in patients with limited-stage SCLC. LncRNA XR_429159.1 is a critical molecule that regulates SCLC metastasis, involved in the neuroepithelial transforming gene 1 (NET1) pathway, and serum levels of this lncRNA are significantly associated with the risk of BM.
本研究的目的是鉴定异常长链非编码RNA（lncRNA），并探讨lncRNA表达模式对局限期小细胞肺癌（SCLC）患者脑转移（BM）风险的预测价值。我们进行了一系列lncRNA和mRNA芯片检测，以检测SCLC伴BM患者外周血单个核细胞中的表达，并将表达模式与无BM患者的表达模式进行比较，以鉴定与BM相关的lncRNA。针对临床数据进行验证，以进一步确认lncRNA与BM之间的关系。应用Kaplan-Meier分析估计BM的累积发生率，并使用对数秩检验分析组间差异。基于lncRNA和mRNA芯片检测，BM组和非BM组之间67种lncRNA（27种上调和40种下调）和47种mRNA（20种上调和27种下调）的表达存在显著差异（倍数变化≥2.0，P值≤0.05）。通过定量实时聚合酶链反应（qRT-PCR）验证了4种lncRNA，以确认芯片数据的准确性，11对患者（11例有BM患者和11例无BM患者）的结果显示，低水平LncRNA XR_429159.1表达是BM的高危因素。进一步的临床数据显示，25例LncRNA XR_429159.1低水平表达患者中，1年时BM的发生率为31%，而18例LncRNA XR_429159.1高水平表达患者中为14.3%（P = 0.035）。我们目前的研究确定lncRNA XR_429159.1的低水平表达是局限期SCLC患者BM的高危因素。LncRNA XR_429159.1是调节SCLC转移的关键分子，参与神经上皮转化基因1（NET1）途径，该lncRNA的血清水平与BM风险显著相关。
