Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Ultrasound Diagnosis Department, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Thorac Cancer. 2021 Mar;12(6):737-745. doi: 10.1111/1759-7714.13833. Epub 2021 Jan 21.
This study aimed to investigate the diagnostic and prognostic role of tumor-educated leukocytes (TELs) mRNA in Chinese patients with non-small cell lung cancer (NSCLC).
The TELs collected underwent total RNA isolation. RNA-sequencing (RNA-seq) technology was used to analyze the transcriptome of the TELs. The mRNA expression levels of differential genes were analyzed by RT-qPCR. Statistical analyses were performed using Prism and SPSS by Mann-Whitney nonparametric test, Kruskal-Wallis test and one-way ANOVA.
We used RNA-seq technology to screen 95 differential genes (DEGs) from seven NSCLC and four controls, wherein 15 genes were upregulated, and 80 were downregulated. Of these, four genes were selected for further analysis, wherein one was upregulated (GPX1) and three were downregulated (BCL9L, MAP3K7CL, PCSK7). RT-qPCR was performed in 431 samples (237 NSCLC, 194 healthy donors). The four-gene panel showed significant differences (p < 0.001) in the expression levels between NSCLC and healthy samples. ROC curves of the panel revealed an AUC of 0.803, with a sensitivity of 73.8% and specificity of 75.3%. GPX1, BCL9L and PCSK7 genes distinguished early-stage NSCLC patients from healthy group (p < 0.05). When the three genes were combined to diagnose early-stage NSCLC, the diagnostic efficacy was 0.772, sensitivity was 73.7%, and specificity was 72.2%. In addition, the downregulated gene BCL9L was associated with chemotherapeutic effect.
The present study provided a systematic description of gene expression profiling in the TELs. It is worth noting that these four genes may be potential candidate genes for NSCLC diagnostic biomarkers and provide a basis for further biological and functional studies.
本研究旨在探讨肿瘤源性白细胞（TEL）mRNA 在中国人非小细胞肺癌（NSCLC）中的诊断和预后作用。
收集 TEL 进行总 RNA 分离。采用 RNA 测序（RNA-seq）技术分析 TEL 的转录组。采用 RT-qPCR 分析差异基因的 mRNA 表达水平。采用 Prism 和 SPSS 统计分析 Mann-Whitney 非参数检验、Kruskal-Wallis 检验和单因素方差分析。
我们使用 RNA-seq 技术从 7 例 NSCLC 和 4 例对照中筛选出 95 个差异基因（DEGs），其中 15 个基因上调，80 个基因下调。其中，有 4 个基因进一步分析，其中一个基因上调（GPX1），三个基因下调（BCL9L、MAP3K7CL、PCSK7）。在 431 例样本（237 例 NSCLC，194 例健康供体）中进行 RT-qPCR。四基因组合在 NSCLC 和健康样本之间的表达水平上有显著差异（p<0.001）。该组合的 ROC 曲线显示 AUC 为 0.803，灵敏度为 73.8%，特异性为 75.3%。GPX1、BCL9L 和 PCSK7 基因可区分早期 NSCLC 患者与健康组（p<0.05）。当这三个基因联合诊断早期 NSCLC 时，诊断效能为 0.772，灵敏度为 73.7%，特异性为 72.2%。此外，下调基因 BCL9L 与化疗疗效相关。
本研究系统描述了 TEL 中的基因表达谱。值得注意的是，这四个基因可能是非小细胞肺癌诊断生物标志物的潜在候选基因，并为进一步的生物学和功能研究提供了基础。
