Duan Fangfang, Wang Weisen, Zhai Wenyu, Wang Junye, Zhao Zerui, Zheng Lie, Rao Bingyu, Zhou Yuheng, Long Hao, Lin Yaobin
Department of Medical Oncology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Front Genet. 2022 Dec 14;13:1078790. doi: 10.3389/fgene.2022.1078790. eCollection 2022.
There is still no ideal predictive biomarker for immunotherapy response among patients with non-small cell lung cancer. Costimulatory molecules play a role in anti-tumor immune response. Hence, they can be a potential biomarker for immunotherapy response. The current study comprehensively investigated the expression of costimulatory molecules in lung squamous carcinoma (LUSC) and identified diagnostic biomarkers for immunotherapy response. The costimulatory molecule gene expression profiles of 627 patients were obtained from the The Cancer Genome Atlas, GSE73403, and GSE37745 datasets. Patients were divided into different clusters using the k-means clustering method and were further classified into two discrepant tumor microenvironment (TIME) subclasses (hot and cold tumors) according to the immune score of the ESTIMATE algorithm. A high proportion of activated immune cells, including activated memory CD4 T cells, CD8 T cells, and M1 macrophages. Five CMGs (FAS, TNFRSF14, TNFRSF17, TNFRSF1B, and TNFSF13B) were considered as diagnostic markers using the Least Absolute Shrinkage and Selection Operator and the Support Vector Machine-Recursive Feature Elimination machine learning algorithms. Based on the five CMGs, a diagnostic nomogram for predicting individual tumor immune microenvironment subclasses in the TCGA dataset was developed, and its predictive performance was validated using GSE73403 and GSE37745 datasets. The predictive accuracy of the diagnostic nomogram was satisfactory in all three datasets. Therefore, it can be used to identify patients who may benefit more from immunotherapy.
在非小细胞肺癌患者中,仍然没有理想的免疫治疗反应预测生物标志物。共刺激分子在抗肿瘤免疫反应中发挥作用。因此,它们可能是免疫治疗反应的潜在生物标志物。本研究全面调查了肺鳞状细胞癌(LUSC)中共刺激分子的表达,并确定了免疫治疗反应的诊断生物标志物。从癌症基因组图谱、GSE73403和GSE37745数据集中获取了627例患者的共刺激分子基因表达谱。使用k均值聚类方法将患者分为不同的簇,并根据ESTIMATE算法的免疫评分进一步分为两个不同的肿瘤微环境(TIME)亚类(热肿瘤和冷肿瘤)。有高比例的活化免疫细胞,包括活化的记忆CD4 T细胞、CD8 T细胞和M1巨噬细胞。使用最小绝对收缩和选择算子以及支持向量机递归特征消除机器学习算法,将五个共刺激分子基因(FAS、TNFRSF14、TNFRSF17、TNFRSF1B和TNFSF13B)视为诊断标志物。基于这五个共刺激分子基因,开发了一种用于预测TCGA数据集中个体肿瘤免疫微环境亚类的诊断列线图,并使用GSE73403和GSE37745数据集验证了其预测性能。诊断列线图在所有三个数据集中的预测准确性都令人满意。因此,它可用于识别可能从免疫治疗中获益更多的患者。