Cui Yanan, Zhang Pengpeng, Liang Xiao, Xu Jiali, Liu Xinyin, Wu Yuemin, Zhang Junling, Wang Wei, Zhang Fang, Guo Renhua
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University Nanjing, Jiangsu, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University Nanjing, Jiangsu, China.
Am J Cancer Res. 2022 Apr 15;12(4):1766-1783. eCollection 2022.
Kinase insert domain receptor (KDR) activation is associated with the immunosuppressive microenvironment. However, the efficacy of immunotherapy in patients with mutations is still unclear. To investigate the relationship between gene mutations and the prognosis of pan-cancer, and whether immune checkpoint inhibitors (ICIs) may improve the prognosis of patients with mutations, we analyzed public cohorts of pan-cancer immunotherapeutic patients including genomic and clinical data.Further analysis was performed on an internal validation data set including 67 non-small cell lung cancer. Through bioinformatics analysis, potential mechanism was studied in TCGA data. We found better responses to ICIs in patients with mutation from pan-cancer public datasets (objective response rate [ORR], 45.0% vs 25.1%, =0.0058; progression-free survival [PFS], P=0.039, HR=0.586, 95% CI 0.353-0.973) and validation cohort (overall survival (OS), P=0.05, HR=0.62; 95% CI, 0.38-1.00). Our NSCLC cohort verified the value of mutation in predicting better clinical outcomes, including ORR (70.0% vs 22.81%, P=0.0057) and PFS (HR=0.158; 95% CI, 0.045-0.773, P=0.007). mutation was associated with tumor mutation burden high, neoantigen burden and immune cellular activities. Meanwhile, mutation was indicative of an immune-hot status, characterized by higher expression of PD-L1 and abundance of cytotoxic lymphocytes. mutations may be potential positive predictors for pan-cancer received ICIs.
激酶插入结构域受体（KDR）激活与免疫抑制微环境相关。然而，免疫疗法在有该突变患者中的疗效仍不明确。为了研究该基因突变与泛癌预后之间的关系，以及免疫检查点抑制剂（ICIs）是否可改善有该突变患者的预后，我们分析了包括基因组和临床数据的泛癌免疫治疗患者公共队列。对包含67例非小细胞肺癌的内部验证数据集进行了进一步分析。通过生物信息学分析，在TCGA数据中研究了潜在机制。我们发现，泛癌公共数据集中有该突变的患者对ICIs反应更好（客观缓解率[ORR]，45.0%对25.1%，P = 0.0058；无进展生存期[PFS]，P = 0.039，HR = 0.586，95%置信区间0.353 - 0.973）以及验证队列（总生存期[OS]，P = 0.05，HR = 0.62；95%置信区间，0.38 - 1.00）。我们的非小细胞肺癌队列验证了该突变在预测更好临床结局方面的价值，包括ORR（70.0%对22.81%，P = 0.0057）和PFS（HR = 0.158；95%置信区间，0.045 - 0.773，P = 0.007）。该突变与肿瘤突变负荷高、新抗原负荷和免疫细胞活性相关。同时，该突变表明处于免疫热状态，其特征为PD - L1表达较高和细胞毒性淋巴细胞丰富。该突变可能是接受ICIs的泛癌潜在阳性预测指标。
