Department of Medical Oncology, Fujian Medical University Union Hospital, No. 29 Xinquan Street, Fuzhou, 350000, Fujian, China.
Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Jin'an District, Fuzhou, 350000, Fujian, China.
Sci Rep. 2023 Aug 17;13(1):13415. doi: 10.1038/s41598-023-40662-z.
T-cell exhaustion (Tex) is considered to be a reason for immunotherapy resistance and poor prognosis in lung adenocarcinoma. Therefore, we used weighted correlation network analysis to identify Tex-related genes in the cancer genome atlas (TCGA). Unsupervised clustering approach based on Tex-related genes divided patients into cluster 1 and cluster 2. Then, we utilized random forest and the least absolute shrinkage and selection operator to identify nine key genes to construct a riskscore. Patients were classified as low or high-risk groups. The multivariate cox analysis showed the riskscore was an independent prognostic factor in TCGA and GSE72094 cohorts. Moreover, patients in cluster 2 with high riskscore had the worst prognosis. The immune response prediction analysis showed the low-risk group had higher immune, stromal, estimate scores, higher immunophenscore (IPS), and lower tumor immune dysfunction and exclusion score which suggested a better response to immune checkpoint inhibitors (ICIs) therapy in the low-risk group. In the meantime, we included two independent immunotherapy cohorts that also confirmed a better response to ICIs treatment in the low-risk group. Besides, we discovered differences in chemotherapy and targeted drug sensitivity between two groups. Finally, a nomogram was built to facilitate clinical decision making.
T 细胞耗竭(Tex)被认为是肺腺癌免疫治疗耐药和预后不良的原因。因此,我们使用加权相关网络分析(weighted correlation network analysis)在癌症基因组图谱(TCGA)中识别与 Tex 相关的基因。基于与 Tex 相关的基因的无监督聚类方法(unsupervised clustering approach)将患者分为聚类 1 和聚类 2。然后,我们利用随机森林(random forest)和最小绝对收缩和选择算子(least absolute shrinkage and selection operator)来识别九个关键基因,构建风险评分(riskscore)。患者被分为低风险或高风险组。多变量 Cox 分析表明,风险评分是 TCGA 和 GSE72094 队列中的独立预后因素。此外,风险评分高的聚类 2 患者预后最差。免疫反应预测分析表明,低风险组具有更高的免疫、基质、估计评分(estimate scores),更高的免疫表型评分(immunophenscore,IPS),以及更低的肿瘤免疫功能障碍和排斥评分(tumor immune dysfunction and exclusion score),这表明低风险组对免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)治疗的反应更好。同时,我们纳入了两个独立的免疫治疗队列,也证实了低风险组对 ICI 治疗的反应更好。此外,我们发现两组之间在化疗和靶向药物敏感性方面存在差异。最后,构建了一个列线图(nomogram),以方便临床决策。
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