DNA methylation-based immune response signature improves patient diagnosis in multiple cancers (Cohort 2). Homo sapiens

Breast cancer (BC) is one of the most common and deadliest malignancies in women worldwide. Tumor immune response is increasingly recognized to be associated with better clinical outcome in breast and other cancers. However, the quantitative evaluation of the tumor immune response by measuring tumor-infiltrating lymphocytes (TILs) remains challenging, since it relies on subjective measurements, which are limited in accuracy and reproducibility. In this study, we sought to identify a set of DNA methylation markers (MeTIL signature) that better recapitulate the evaluation of TILs and their impact on long-term outcome in BC. We showed that the MeTIL score measures TIL distributions in a more robust and sensitive manner than conventional pathological TIL counts and that this translates into better prediction of survival and response to chemotherapy in BC. We demonstrated that the MeTIL score can be determined in low amounts of DNA from FFPE tumor tissue by bisulfite pyrosequencing allowing for the fast and cost-efficient evaluation of TILs in the clinical setting. Overall design: Bisulphite converted DNA of the 119 samples from the Cohort 2 were hybridized to the Illumina Infinium 450k Human Methylation Beadchip

乳腺癌（Breast Cancer, BC）是全球女性最常见且致死率最高的恶性肿瘤之一。肿瘤免疫应答愈发被认为与乳腺癌及其他癌症的良好临床结局密切相关。然而，通过检测肿瘤浸润淋巴细胞（Tumor-Infiltrating Lymphocytes, TILs）来定量评估肿瘤免疫应答仍颇具挑战，因为该方法依赖主观测量，其准确性和可重复性均存在局限。本研究旨在筛选出一组DNA甲基化标志物（MeTIL signature），以更精准地复现TILs的评估结果及其对乳腺癌远期预后的影响。研究表明，相较于传统的病理学TIL计数法，MeTIL评分能够以更稳健、更灵敏的方式量化TIL的分布情况，且该评分可更准确地预测乳腺癌患者的生存情况及化疗应答反应。本研究证实，可通过亚硫酸氢盐焦磷酸测序法，对福尔马林固定石蜡包埋（Formalin-Fixed Paraffin-Embedded, FFPE）肿瘤组织中微量提取的DNA进行MeTIL评分检测，从而实现在临床场景中快速且经济高效地评估TILs水平。整体实验设计：将队列2中119份样本的亚硫酸氢盐转化DNA，与Illumina Infinium 450K人类甲基化芯片进行杂交。