Division of Pulmonary and Critical Care Medicine, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
Expert Rev Mol Diagn. 2022 Sep;22(9):905-913. doi: 10.1080/14737159.2022.2131396. Epub 2022 Oct 14.
Methylation of cytosine residues resulting in 5-methylcytosine (5-mC) is an important epigenetic modification associated with tumorigenesis. The present study explored the relationship between methylation, prognosis, and immunotherapy of patients suffering from lung squamous cell carcinoma (LUSC).
RNA sequencing data and corresponding clinical information were downloaded, and preprocessed, and unsupervised consistent cluster analysis was used to identify 5-mC-related clusters and gene clusters. 5-mC scores were calculated using principal component analysis, and a Boruta algorithm was used to evaluate the relationship between tumor mutation burden (TMB), immune checkpoint inhibitor response, and prognosis of individual LUSC patients.
: Two 5-mC clusters and three gene clusters with different prognoses were identified. Patients with higher 5-mC scores showed worse prognoses, which was confirmed in multiple cohorts. Some immune-related biological functions and pathways were enriched in the high-5-mC score subtype.
The 5-mC score is a potential biomarker independent of TMB, which can be a decisive factor regarding immune treatment responses. Further, patients with low 5-mC scores may respond better to immunotherapy. The 5-mC score can thus be used as a potential biomarker for the prognosis of LUSC patients and their response to immunotherapy.
胞嘧啶残基的甲基化导致 5-甲基胞嘧啶（5-mC）是与肿瘤发生相关的重要表观遗传修饰。本研究探讨了肺鳞状细胞癌（LUSC）患者甲基化、预后和免疫治疗之间的关系。
下载 RNA 测序数据和相应的临床信息，并进行预处理，使用无监督一致性聚类分析来识别 5-mC 相关聚类和基因聚类。使用主成分分析计算 5-mC 评分，并使用 Boruta 算法评估个体 LUSC 患者的肿瘤突变负担（TMB）、免疫检查点抑制剂反应和预后之间的关系。
确定了两个 5-mC 聚类和三个具有不同预后的基因聚类。5-mC 评分较高的患者预后较差，在多个队列中得到了证实。高 5-mC 评分亚型中富集了一些与免疫相关的生物学功能和途径。
5-mC 评分是一种独立于 TMB 的潜在生物标志物，可能是免疫治疗反应的决定性因素。此外，5-mC 评分较低的患者可能对免疫治疗反应更好。因此，5-mC 评分可以作为 LUSC 患者预后和免疫治疗反应的潜在生物标志物。
