Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, 29208, USA.
Department of Epidemiology and Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Cancer Immunol Immunother. 2020 Sep;69(9):1881-1890. doi: 10.1007/s00262-020-02595-8. Epub 2020 May 5.
Lung adenocarcinoma (LUAD) has become the most frequent histologic type of lung cancer in the past several decades. Recent successes with immune checkpoint blockade therapy have demonstrated that the manipulation of the immune system is a very potent treatment for LUAD. This study aims to explore the role of immune-related genes in the development of LUAD and establish a signature that can predict overall survival for LUAD patients.
To identify the differential expression genes (DEGs) between normal and tumor tissues, we developed an analysis strategy to combine an independent-sample design and a paired-sample design using RNA-seq transcriptomic profiling data of The Cancer Genome Atlas LUAD samples. Further, we selected prognostic markers from DEGs and evaluated their prognostic value in a prediction model.
We identified and validated PD1, PDL1 and CTLA4 genes as prognostic markers, which are well-known immune checkpoints, and revealed two new potential prognostic immune checkpoints for LUAD, HHLA2 (logFC = 2.55, FDR = 1.89 × 10) and VTCN1 (logFC = -2.86, FDR = 1.72 × 10). Furthermore, we identified an 18-gene LUAD prognostic biomarker panel and observed that the classified high-risk group presented a significantly shorter overall survival time (HR = 3.57, p value = 4.07 × 10). The prediction model was validated in five independent high-throughput gene expression datasets.
The identified DEG features may serve as potential biomarkers for prognosis prediction of LUAD patients and immunotherapy. Based on that assumption, we identified a gene expression-based immune signature for lung adenocarcinoma prognosis.
在过去几十年中，肺腺癌 (LUAD) 已成为最常见的肺癌组织学类型。免疫检查点阻断疗法的最新成功表明，免疫系统的调控是 LUAD 非常有效的治疗方法。本研究旨在探讨免疫相关基因在 LUAD 发生发展中的作用，并建立一个可预测 LUAD 患者总生存期的特征签名。
为了鉴定正常组织和肿瘤组织之间的差异表达基因 (DEG)，我们开发了一种分析策略，该策略使用来自癌症基因组图谱 (TCGA) LUAD 样本的 RNA-seq 转录组谱数据，结合独立样本设计和配对样本设计。此外，我们从 DEG 中选择了预后标志物，并在预测模型中评估了其预后价值。
我们鉴定并验证了 PD1、PDL1 和 CTLA4 基因作为预后标志物，这些基因是众所周知的免疫检查点，并揭示了两个 LUAD 的新的潜在预后免疫检查点，HHLA2（logFC=2.55，FDR=1.89×10）和 VTCN1（logFC=-2.86，FDR=1.72×10）。此外，我们鉴定了一个 18 基因 LUAD 预后生物标志物面板，并观察到分类的高风险组的总生存期明显缩短（HR=3.57，p 值=4.07×10）。该预测模型在五个独立的高通量基因表达数据集进行了验证。
所鉴定的 DEG 特征可能作为 LUAD 患者预后预测的潜在生物标志物和免疫治疗的潜在生物标志物。基于这一假设，我们确定了一个基于基因表达的 LUAD 预后免疫特征签名。
