MTDH associates with m6A RNA methylation and predicts cancer response for immune checkpoint treatment.
MTDH associates with m6A RNA methylation and predicts cancer response for immune checkpoint treatment.
复制标题
MTDH 与 m6A RNA 甲基化相关，并预测免疫检查点治疗的癌症反应。
DOI：
10.1016/j.isci.2021.103102
复制
发表时间：
2021-10-22
期刊：
影响因子：
5.8
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Zhang F;Huang H;Qin Y;Chen C;She L;Wang J;Huang D;Tang Q;Liu Y;Zhu G;Zhang X
免疫检查点阻断（ICB）持续提供预后改善，但仅适用于一小部分癌症患者，这是由于连续激活的致癌途径（包括部分由Metadherin （MTDH）驱动的MAPK、Akt和WNT途径）诱导的免疫治疗抵抗。然而，目前还没有研究探讨MTDH在icb治疗的癌症中的潜在作用和机制。在这里，我们系统地探索了来自癌症基因组图谱（TCGA）和独立癌症队列的队列。发现MTDH表达升高与癌症患者较差的总生存率和较差的免疫反应有关。肿瘤浸润性免疫细胞异常和免疫检查点抑制表达与MTDH表达相关。此外，上皮-间质转化、m6a - rna甲基化和MTDH之间的相互作用可能说明MTDH对ICB治疗耐药的潜在机制。尽管未来需要更多的设计实验和试验，但靶向MTDH可能有助于克服多种癌症的免疫治疗耐药性。MTDH与肿瘤免疫环境和检查点表达失调有关MTDH/m6A RNA甲基化/EMT途径可能与免疫治疗耐药有关分子生物学;表达的研究
Immune checkpoint blockade (ICB) persistently provides a prognosis improvement but only in a small fraction of patients with cancer due to immunotherapy resistance induced by the consecutive activated oncogenic pathways, including MAPK, Akt, and WNT pathway partially driven by Metadherin (MTDH). However, there is no study to investigate the potential role and mechanisms of MTDH in ICB-treated cancers. Here, we systematically explored the cohorts from The Cancer Genome Atlas (TCGA) and independent cancer cohorts. Elevated MTDH expression was founded to associate with a worse overall survival and poorer immune response in patients with cancer. Dysregulated tumor-infiltrating immune cells and inhibitory immune checkpoint expression were correlated with MTDH expression. Furthermore, the mutual interactions between epithelial-to-mesenchymal-transition, m6A-RNA-methylation, and MTDH may illustrate the potential mechanisms of MTDH resistant to ICB treatment. Although more designed experiments and trials are needed in the future, targeting MTDH may help to overcome immunotherapy resistance in a wide range of cancers. MTDH associates with prognosis and immunotherapy response for patients with cancer MTDH associates with dysregulated tumor immune environment and checkpoint expression The MTDH/m6A RNA methylation/EMT pathway may contribute to immunotherapy resistance Biological sciences; Molecular biology; Expression study
登录
查看更多内容
影响因子：
64.8
作者：
Helmink BA;Reddy SM;Gao J;Zhang S;Basar R;Thakur R;Yizhak K;Sade-Feldman M;Blando J;Han G;Gopalakrishnan V;Xi Y;Zhao H;Amaria RN;Tawbi HA;Cogdill AP;Liu W;LeBleu VS;Kugeratski FG;Patel S;Davies MA;Hwu P;Lee JE;Gershenwald JE;Lucci A;Arora R;Woodman S;Keung EZ;Gaudreau PO;Reuben A;Spencer CN;Burton EM;Haydu LE;Lazar AJ;Zapassodi R;Hudgens CW;Ledesma DA;Ong S;Bailey M;Warren S;Rao D;Krijgsman O;Rozeman EA;Peeper D;Blank CU;Schumacher TN;Butterfield LH;Zelazowska MA;McBride KM;Kalluri R;Allison J;Petitprez F;Fridman WH;Sautès-Fridman C;Hacohen N;Rezvani K;Sharma P;Tetzlaff MT;Wang L;Wargo JA
通讯作者：
Wargo JA
影响因子：
37.3
作者：
Chen, Xiaoxiang;Xu, Mu;Wang, Shukui
通讯作者：
Wang, Shukui
影响因子：
11.2
作者：
Akalay, Intissar;Janji, Bassam;Chouaib, Salem
通讯作者：
Chouaib, Salem
DOI：
10.1073/pnas.1918986117
发表时间：
2020-08-18
影响因子：
11.1
作者：
Li, Na;Kang, Yuqi;Rana, Tariq M.
通讯作者：
Rana, Tariq M.
影响因子：
82.9
作者：
Auslander N;Zhang G;Lee JS;Frederick DT;Miao B;Moll T;Tian T;Wei Z;Madan S;Sullivan RJ;Boland G;Flaherty K;Herlyn M;Ruppin E
通讯作者：
Ruppin E