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全面分析卵巢癌中 11 个预后性可变剪接事件与免疫微环境的相互作用。

Comprehensive characterization of 11 prognostic alternative splicing events in ovarian cancer interacted with the immune microenvironment.

机构信息

Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, 250012, People's Republic of China.

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong Province, 250012, People's Republic of China.

出版信息

Sci Rep. 2022 Jan 19;12(1):980. doi: 10.1038/s41598-021-03836-1.

DOI:10.1038/s41598-021-03836-1
PMID:35046435
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8770494/
Abstract

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.

摘要

可变剪接 (AS) 事件在癌症的发生和发展中起着至关重要的作用。我们从 TCGA 数据库和 TCGA SpliceSeq 下载了卵巢癌患者的转录组数据和 PSI 值。总共鉴定出 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。我们进行了单因素和多因素 Cox 回归分析，以确定与生存相关的 AS 事件，并基于 11 个 AS 事件开发了预后模型。分析了低风险和高风险组 OC 患者的免疫细胞和对细胞毒性 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) 阻滞剂的不同反应。在低风险组中发现了 10 种免疫细胞上调。活化 B 细胞、自然杀伤 T 细胞、自然杀伤细胞和调节性 T 细胞与 OC 的生存相关。低风险组的患者对 CTLA-4 和 PD-1 阻滞剂治疗有良好的反应。此外，根据 AS 事件与剪接因子 (SFs) 之间的相关性建立了一个调控网络。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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/a3724bff74a6/41598_2021_3836_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/82af606f41d4/41598_2021_3836_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/f8ea13543b16/41598_2021_3836_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/7217a1f1d68b/41598_2021_3836_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/8196646e723e/41598_2021_3836_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/25e76ab6dc6e/41598_2021_3836_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/a3724bff74a6/41598_2021_3836_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/82af606f41d4/41598_2021_3836_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/52d49bc16435/41598_2021_3836_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/0fe60cb13b87/41598_2021_3836_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/c0131be51c30/41598_2021_3836_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/f8ea13543b16/41598_2021_3836_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/7217a1f1d68b/41598_2021_3836_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/8196646e723e/41598_2021_3836_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/25e76ab6dc6e/41598_2021_3836_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/8770494/a3724bff74a6/41598_2021_3836_Fig9_HTML.jpg

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