Identification of mRNA vaccines and conserved ferroptosis related immune landscape for individual precision treatment in bladder cancer.
Identification of mRNA vaccines and conserved ferroptosis related immune landscape for individual precision treatment in bladder cancer.
复制标题
DOI：
10.1186/s40537-022-00641-z
复制
发表时间：
2022
影响因子：
8.1
通讯作者：
中科院分区：
文献类型：
--
作者：
本研究的目的是确定膀胱癌（BCa）中铁凋亡诱导的肿瘤微环境（FeME）景观，用于mRNA疫苗开发和选择合适的患者进行精确治疗。从TCGA-BLCA、3个GEO数据库和IMvigor 210队列中提取1216例BCa患者的基因表达谱和临床信息。我们基于290个铁凋亡相关基因（FRG）全面建立了1216个BCa样本的FeME景观，并将这些调控模式与TME细胞浸润特征系统地关联起来。此外，我们还通过患者的铁凋亡危险指数（FRI）来预测BCa的预后，以便进行精确的治疗。在BCa中鉴定出6种与不良预后和抗原呈递细胞浸润相关的过度表达和突变的肿瘤抗原。此外，我们证明了个体肿瘤内FeME的评估可以预测肿瘤炎症的阶段、亚型、遗传变异和患者预后。然后，5-lncRNA签名被挖掘以产生FRI。低FRI还与突变负荷增加、预后更好和对抗PD-L1免疫治疗的反应增强有关。此外，免疫治疗队列证实FRI较低的患者表现出显著的治疗优势和临床获益。TFRC、SCD、G6 PD、FADS 2、SQLE和SLC 3A 2是开发抗BCa mRNA疫苗的有效抗原。FRI的建立将有助于提高我们对TME浸润特征的认识，指导更有效的免疫治疗策略，并选择合适的患者进行肿瘤疫苗治疗。在线版本包含补充材料，可通过10.1186/s40537-022-00641-z获得。
The aim of this study was to identify the ferroptosis induced tumor microenvironment (FeME) landscape in bladder cancer (BCa) for mRNA vaccine development and selecting suitable patients for precision treatment. Gene expression profiles and clinical information of 1216 BCa patients were extracted from TCGA-BLCA, three GEO databases and IMvigor210 cohort. We comprehensively established the FeME landscape of 1216 BCa samples based on 290 ferroptosis related genes (FRGs), and systematically correlated these regulation patterns with TME cell-infiltrating characteristics. Besides, we identified the patients’ ferroptosis risk index (FRI) to predict the prognosis of BCa for precise treatment. Six over-expressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in BCa. Furthermore, we demonstrated the evaluation of FeME within individual tumors could predict stages of tumor inflammation, subtypes, genetic variation, and patient prognosis. Then, 5-lncRNA signature was mined to produce the FRI. Low FRI was also linked to increased mutation load, better prognosis and enhanced response to anti-PD-L1 immunotherapy. Besides, an immunotherapy cohort confirmed patients with lower FRI demonstrated significant therapeutic advantages and clinical benefits. TFRC, SCD, G6PD, FADS2, SQLE, and SLC3A2 are potent antigens for developing anti-BCa mRNA vaccine. Establishment of FRI will contribute to enhancing our cognition of TME infiltration characterization and guiding more effective immunotherapy strategies and selecting appropriate patients for tumor vaccine therapy. The online version contains supplementary material available at 10.1186/s40537-022-00641-z.
登录
查看更多内容
影响因子：
5.3
作者：
Li X;Jin F;Li Y
通讯作者：
Li Y
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
EGLN1/c-Myc 诱导的淋巴特异性解旋酶通过脂质代谢基因表达变化抑制铁死亡
影响因子：
12.4
作者：
Jiang Y;Mao C;Yang R;Yan B;Shi Y;Liu X;Lai W;Liu Y;Wang X;Xiao D;Zhou H;Cheng Y;Yu F;Cao Y;Liu S;Yan Q;Tao Y
通讯作者：
Tao Y
影响因子：
4.6
作者：
Hajiran, A.;Chakiryan, N.;Manley, B.
通讯作者：
Manley, B.
影响因子：
64.8
作者：
Mariathasan S;Turley SJ;Nickles D;Castiglioni A;Yuen K;Wang Y;Kadel EE III;Koeppen H;Astarita JL;Cubas R;Jhunjhunwala S;Banchereau R;Yang Y;Guan Y;Chalouni C;Ziai J;Şenbabaoğlu Y;Santoro S;Sheinson D;Hung J;Giltnane JM;Pierce AA;Mesh K;Lianoglou S;Riegler J;Carano RAD;Eriksson P;Höglund M;Somarriba L;Halligan DL;van der Heijden MS;Loriot Y;Rosenberg JE;Fong L;Mellman I;Chen DS;Green M;Derleth C;Fine GD;Hegde PS;Bourgon R;Powles T
通讯作者：
Powles T