Xue Zhengfa, Yang Shuxin, Luo Yun, He Ming, Qiao Huimin, Peng Wei, Tong Suxin, Hong Guini, Guo You
Medical Big Data and Bioinformatics Research Centre, First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
Department of Computer Science and Technology, School of Electronic and Information Engineering, Xi'an Jiao Tong University, Xi'an, China.
Front Oncol. 2022 Sep 29;12:993726. doi: 10.3389/fonc.2022.993726. eCollection 2022.
Accumulating evidence indicates that neoadjuvant chemoradiotherapy(nCRT) success has an immune-associated constituent in locally advanced rectal cancer (LARC). The immune-associated configuration of the tumor microenvironment associated with responses to treatment was explored in LARC in this study.
A novel analytic framework was developed based on within-sample relative expression orderings for identifying tumor immune-associated gene pairs and identified an immuno-score signature from bulk transcriptome profiling analysis of 200 LARC patients. And sequencing and microarray analysis of gene expression was conducted to investigate the association between the signature and response to nCRT, immunotherapy, and cell function of CD4 and CD8. The results were validated using 111 pretreated samples from publicly available datasets in multiple aspects and survival analyses.
The immuno-score signature of 18 immune-related gene pairs (referred to as IPS) was validated on bulk microarray and RNA-Seq data. According to the model's immune score, LARC patients were divided into high- and low-score groups. The patients with high-score were greater sensitivity to nCRT and immunotherapy, gaining a significantly improved prognosis. In addition, the immune-score gene pair signature was associated with type I anti-tumor T cell responses, positive regulators of T cell functions, and chromosomal instability while reflecting differences between CD8+ T cell subtypes.
The immuno-score signature underlines a key role of tumor immune components in nCRT response, and predicts the prognosis of LARC patients as well.
越来越多的证据表明，新辅助放化疗（nCRT）在局部晚期直肠癌（LARC）治疗中的成功具有免疫相关成分。本研究在LARC中探索了与治疗反应相关的肿瘤微环境的免疫相关特征。
基于样本内相对表达排序开发了一种新的分析框架，用于识别肿瘤免疫相关基因对，并从200例LARC患者的批量转录组分析中确定了免疫评分特征。并进行基因表达的测序和微阵列分析，以研究该特征与nCRT反应、免疫治疗以及CD4和CD8细胞功能之间的关联。结果在多个方面使用来自公开可用数据集的111个预处理样本和生存分析进行了验证。
18个免疫相关基因对的免疫评分特征（称为IPS）在批量微阵列和RNA测序数据上得到验证。根据模型的免疫评分，将LARC患者分为高分和低分两组。高分患者对nCRT和免疫治疗的敏感性更高，预后显著改善。此外，免疫评分基因对特征与I型抗肿瘤T细胞反应、T细胞功能的正调节因子以及染色体不稳定性相关，同时反映了CD8 + T细胞亚型之间的差异。
免疫评分特征强调了肿瘤免疫成分在nCRT反应中的关键作用，并预测了LARC患者的预后。
