A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes.
A Methylation-Based Reclassification of Bladder Cancer Based on Immune Cell Genes.
复制标题
DOI：
10.3390/cancers12103054
复制
发表时间：
2020-10-20
期刊：
影响因子：
5.2
通讯作者：
Vögeli TA
中科院分区：
文献类型：
--
作者：
Luo Q;Vögeli TA
膀胱癌（BC）的发展与免疫细胞浸润高度相关。在这项研究中，我们旨在基于免疫细胞相关的CpG（甲基化）位点构建膀胱癌分子亚型的新分类。分类准确、稳定。根据免疫细胞相关的CpG位点，将BC患者成功分为三种亚型。3个亚组的临床病理特征、免疫细胞分布、检查点表达水平、基质评分、免疫评分、ESTIMATEScore、肿瘤纯度、APC co_inhibition、APC co_stimulation、HLA、MHC class_I、I型ifn_response、II型IFN response、DNA stemness score （DNA干性评分）差异均有统计学意义。具体的基因组改变在亚群之间也不同。高水平的免疫浸润与高水平的甲基化相关。较低的RNA干性评分（RNAss）与较高的免疫浸润相关。第2组对化疗反应较好。三个亚组的抗癌靶向药物治疗效果不同。背景：膀胱癌与免疫细胞浸润高度相关。本研究旨在建立基于免疫细胞相关CpG位点的BC分子亚型的新分类。方法：从前人的研究中获得28种免疫细胞的基因。然后，获得与免疫细胞相关基因对应的甲基化位点。在正常样本和膀胱癌样本之间鉴定了差异甲基化位点（dms）。对差异甲基化位点进行无监督聚类分析，将这些位点划分为几个亚型。然后，探讨不同亚型的潜在机制。结果：膀胱癌患者分为三组。聚类3亚型预后最好。第1组预后最差。免疫细胞分布、检查点表达水平、基质评分、免疫评分、ESTIMATEScore、肿瘤纯度、APC co_inhibition、APC co_stimulation、HLA、MHC class_I、I型IFN Response、II型IFN Response、dnas在3个亚组间存在显著差异。基因组改变的分布也不同。结论：所建立的分类方法准确、稳定。根据免疫细胞相关的CpG位点，BC患者可分为三种亚型。特定的生物信号通路、免疫机制和基因组改变在三个亚组中有所不同。高水平的免疫浸润与高水平的甲基化相关。较低的RNAss与较高的免疫浸润有关。肿瘤内免疫微环境的研究可能为乳腺癌的治疗提供新的视角。
Bladder cancer (BC) development is highly related to immune cell infiltration. In this study, we aimed to construct a new classification of bladder cancer molecular subtypes based on immune-cell-associated CpG(Methylation) sites. The classification was accurate and stable. BC patients were successfully divided into three subtypes based on the immune-cell-associated CpG sites. The clinicopathologic features, distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN_respons, Type II IFN response, and DNA stemness score (DNAss) presented significant differences among the three subgroups. The specific genomic alteration was also different across subgroups. High-level immune infiltration showed a correlation with high-level methylation. A lower RNA stemness score (RNAss) was associated with higher immune infiltration. Cluster 2 demonstrated a better response to chemotherapy. The anti-cancer targeted drug therapy results are different among the three subgroups. Background: Bladder cancer is highly related to immune cell infiltration. This study aimed to develop a new classification of BC molecular subtypes based on immune-cell-associated CpG sites. Methods: The genes of 28 types of immune cells were obtained from previous studies. Then, methylation sites corresponding to immune-cell-associated genes were acquired. Differentially methylated sites (DMSs) were identified between normal samples and bladder cancer samples. Unsupervised clustering analysis of differentially methylated sites was performed to divide the sites into several subtypes. Then, the potential mechanism of different subtypes was explored. Results: Bladder cancer patients were divided into three groups. The cluster 3 subtype had the best prognosis. Cluster 1 had the poorest prognosis. The distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co_inhibition, APC co_stimulation, HLA, MHC class_I, Type I IFN Response, Type II IFN Response, and DNAss presented significant differences among the three subgroups. The distribution of genomic alterations was also different. Conclusions: The proposed classification was accurate and stable. BC patients could be divided into three subtypes based on the immune-cell-associated CpG sites. Specific biological signaling pathways, immune mechanisms, and genomic alterations were varied among the three subgroups. High-level immune infiltration was correlated with high-level methylation. The lower RNAss was associated with higher immune infiltration. The study of the intratumoral immune microenvironment may provide a new perspective for BC therapy.
登录
查看更多内容
将固体癌的归巢：使用CAR T细胞疗法的血管检查点。
影响因子：
3.9
作者：
Ager A;Watson HA;Wehenkel SC;Mohammed RN
通讯作者：
Mohammed RN
影响因子：
4.3
作者：
Chen, Yun-Ching;Elnitski, Laura
通讯作者：
Elnitski, Laura
影响因子：
4.6
作者：
Chakraborty S;Panda AK;Bose S;Roy D;Kajal K;Guha D;Sa G
通讯作者：
Sa G
影响因子：
4.7
作者：
Bagaria, Sanjay P.;Gatalica, Zoran;Joseph, Richard W.
通讯作者：
Joseph, Richard W.
影响因子：
4.3
作者：
Chen J;Guo XZ;Li HY;Zhao JJ;Xu WD
通讯作者：
Xu WD