Wang Rong, Zhang Xing, He Changshou, Guo Wei
Respiratory department, Shanxi Cancer Hospital, Taiyuan, China.
Department of Oncology, HaploX Biotechnology, Shenzhen, China.
Front Genet. 2023 Apr 13;14:1156322. doi: 10.3389/fgene.2023.1156322. eCollection 2023.
Brain metastasis, with an incidence of more than 30%, is a common complication of non-small cell lung cancer (NSCLC). Therefore, there is an urgent need for an assessment method that can effectively predict brain metastases in NSCLC and help understand its mechanism. GSE30219, GSE31210, GSE37745, and GSE50081 datasets were downloaded from the GEO database and integrated into a dataset (GSE). The integrated dataset was divided into the training and test datasets. TCGA-NSCLC dataset was regarded as an independent verification dataset. Here, the limma R package was used to identify the differentially expression genes (DEGs). Importantly, the RiskScore model was constructed using univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis. Moreover, we explored in detail the tumor mutational signature, immune signature, and sensitivity to treatment of brain metastases in NSCLC. Finally, a nomogram was built using the rms package. First, 472 DEGs associated with brain metastases in NSCLC were obtained, which were closely associated with cancer-associated pathways. Interestingly, a RiskScore model was constructed using 11 genes from 472 DEGs, and the robustness was confirmed in GSE test, entire GSE, and TCGA datasets. Samples in the low RiskScore group had a higher gene mutation score and lower immunoinfiltration status. Moreover, we found that the patients in the low RiskScore group were more sensitive to the four chemotherapy drugs. In addition, the predictive nomogram model was able to effectively predict the outcome of patients through appropriate RiskScore stratification. The prognostic RiskScore model we established has high prediction accuracy and survival prediction ability for brain metastases in NSCLC.
脑转移是非小细胞肺癌(NSCLC)常见的并发症,发生率超过30%。因此,迫切需要一种能够有效预测NSCLC脑转移并有助于了解其机制的评估方法。从GEO数据库下载了GSE30219、GSE31210、GSE37745和GSE50081数据集,并将其整合为一个数据集(GSE)。将整合后的数据集分为训练集和测试集。TCGA-NSCLC数据集被视为独立验证集。在此,使用limma R包来识别差异表达基因(DEG)。重要的是,使用单变量Cox回归分析和最小绝对收缩和选择算子(LASSO)分析构建风险评分(RiskScore)模型。此外,我们详细探讨了NSCLC脑转移的肿瘤突变特征、免疫特征和对治疗的敏感性。最后,使用rms包构建列线图。首先,获得了472个与NSCLC脑转移相关的DEG,这些基因与癌症相关通路密切相关。有趣的是,使用472个DEG中的11个基因构建了RiskScore模型,并在GSE测试集、整个GSE数据集和TCGA数据集中证实了其稳健性。低RiskScore组的样本具有较高的基因突变评分和较低的免疫浸润状态。此外,我们发现低RiskScore组的患者对四种化疗药物更敏感。此外,预测性列线图模型能够通过适当的RiskScore分层有效预测患者的预后。我们建立的预后RiskScore模型对NSCLC脑转移具有较高的预测准确性和生存预测能力。