RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
英文原题:Comprehensive characterization of 11 prognostic alternative splicing events in ovarian cancer interacted with the immune microenvironment.
Comprehensive characterization of 11 prognostic alternative splicing events in ovarian cancer interacted with the immune microenvironment.
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可变剪接(AS)事件在肿瘤发生和进展中起着至关重要的作用。从TCGA数据库和TCGA SpliceSeq下载了卵巢癌患者的转录组数据和Percent Spliced In(PSI)值。
我们共鉴定出1472个与卵巢浆液性囊腺癌(OC)生存相关的AS事件,其中外显子跳跃(ES)是最重要的类型。进行单因素和多因素Cox回归分析以鉴定与生存相关的AS事件,并基于11个AS事件构建了预后模型。分析了OC患者低风险组和高风险组中免疫细胞以及对细胞毒性T淋巴细胞相关抗原4(CTLA-4)和程序性细胞死亡蛋白1(PD-1)阻断剂的不同反应。发现低风险组中有十种免疫细胞上调。活化B细胞、自然杀伤T细胞、NK 细胞和调节性T细胞与OC的生存相关。低风险组患者对CTLA-4和PD-1阻断剂治疗反应良好。
此外,根据AS事件与剪接因子(SFs)之间的相关性建立了调控网络。本研究为OC的潜在机制提供了有价值的见解。与免疫系统相关的AS事件可能是潜在的治疗靶点。
Alternative splicing (AS) events play a crucial role in the tumorigenesis and progression of cancer. Transcriptome data and Percent Spliced In (PSI) values of ovarian cancer patients were downloaded from TCGA database and TCGA SpliceSeq. Totally we identified 1472 AS events that were associated with survival of ovarian serous cystadenocarcinoma (OC) and exon skipping (ES) was the most important type. Univariate and multivariate Cox regression analysis were performed to identify survival-associated AS events and developed the prognostic model based on 11-AS events.
The immune cells and different response to cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) blockers in low-risk and high-risk group of OC patients were analyzed. Ten kinds of immune cells were found up-regulated in low-risk group. Activated B cell, natural killer T cell, natural killer cell and regulatory T cell were associated with survival of OC. The patients in low-risk group had good response to CTLA-4 and PD-1 blockers treatment.
Moreover, a regulatory network was established according to the correlation between AS events and splicing factors (SFs). The present study provided valuable insights into the underlying mechanisms of OC. AS events that were correlated with the immune system might be potential therapeutic targets.
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