基于免疫相关基因 FGFR4 的列线图在免疫检查点抑制剂敏感的晚期非小细胞肺癌患者中的构建。

Development of nomogram based on immune-related gene FGFR4 for advanced non-small cell lung cancer patients with sensitivity to immune checkpoint inhibitors.

机构信息

Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, 266003, China.

Department of Oncology, TCM-Integrated Hospital of Southern Medical University, Southern Medical University, Guangzhou, 510000, China.

出版信息

J Transl Med. 2021 Jan 6;19(1):22. doi: 10.1186/s12967-020-02679-0.

INTRODUCTION

Immune checkpoint inhibitors (ICIs) have become a frontier in the field of clinical technology for advanced non-small cell lung cancer (NSCLC). Currently, the predictive biomarker of ICIs mainly including the expression of PD-L1, TMB, TIICs, MMR and MSI-H. However, there are no official biomarkers to guide the treatment of ICIs and to determine the prognosis. Therefore, it is essential to explore a systematic nomogram to predict the prognosis of ICIs treatment in NSCLC METHODS: In this work, we obtained gene expression and clinical data of NSCLC patients from the TCGA database. Immune-related genes (IRGs) were downloaded from the ImmPort database. The detailed clinical annotation and response data of 240 advanced NSCLC patients who received ICIs treatment were obtained from the cBioPortal for Cancer Genomics. Kaplan-Meier survival analysis was used to perform survival analyses, and selected clinical variables to develop a novel nomogram. The prognostic significance of FGFR4 was validated by another cohort in cBioPortal for Cancer Genomics.

RESULTS

3% of the NSCLC patients harbored FGFR4 mutations. The mutation of FGFR4 were confirmed to be associated with PD-L1, and TMB. Patients harbored FGFR4 mutations were found to have a better prolonged progression-free survival (PFS) to ICIs treatment (FGFR4: P = 0.0209). Here, we built and verified a novel nomogram to predict the prognosis of ICIs treatment for NSCLC patients.

CONCLUSION

Our results showed that FGFR4 could serve as novel biomarkers to predict the prognosis of ICIs treatment of advanced NSCLC. Our systematic prognostic nomogram showed a great potential to predict the prognosis of ICIs for advanced NSCLC patients.

简介

免疫检查点抑制剂（ICIs）已成为晚期非小细胞肺癌（NSCLC）临床技术领域的前沿。目前，ICI 的预测生物标志物主要包括 PD-L1 表达、TMB、TIICs、MMR 和 MSI-H。然而，目前还没有官方的生物标志物来指导 ICI 的治疗和确定预后。因此，探索一种系统的列线图来预测 NSCLC 患者接受 ICI 治疗的预后至关重要。

方法

在这项工作中，我们从 TCGA 数据库中获得了 NSCLC 患者的基因表达和临床数据。从 ImmPort 数据库下载了免疫相关基因（IRGs）。从 cBioPortal for Cancer Genomics 获得了 240 名接受 ICI 治疗的晚期 NSCLC 患者的详细临床注释和反应数据。Kaplan-Meier 生存分析用于进行生存分析，并选择临床变量来开发新的列线图。在 cBioPortal for Cancer Genomics 中，另一个队列验证了 FGFR4 的预后意义。

结果

3%的 NSCLC 患者存在 FGFR4 突变。FGFR4 突变被证实与 PD-L1 和 TMB 相关。存在 FGFR4 突变的患者发现对 ICI 治疗的无进展生存期（PFS）延长有更好的效果（FGFR4：P=0.0209）。在这里，我们构建并验证了一个新的列线图来预测 NSCLC 患者接受 ICI 治疗的预后。