The Prognostic Value of DNA Methylation, Post-Translational Modifications and Correlated with Immune Infiltrates in Gynecologic Cancers.
The Prognostic Value of DNA Methylation, Post-Translational Modifications and Correlated with Immune Infiltrates in Gynecologic Cancers.
复制标题
DNA 甲基化、翻译后修饰及其与妇科癌症免疫浸润的相关性的预后价值
DOI：
10.2147/pgpm.s293399
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发表时间：
2021
影响因子：
1.9
通讯作者：
Guo H
中科院分区：
文献类型：
--
作者：
Shang C;Li Y;Wu Z;Han Q;Zhu Y;He T;Guo H
背景 从 DNA 甲基化、选择性剪接 (AS) 和多腺苷酸化 (APA) 事件的角度描述妇科癌症的预后情况，并研究它们与免疫浸润的相关性。方法利用妇科癌症的甲基化和RNA-seq数据以及相应的临床信息，探讨DNA甲基化变化、AS和APA事件与妇科癌症预后之间的关系。采用 QRT-PCR 和多种生物信息学工具构建基因相互作用网络并探索免疫浸润。结果经 qrt-PCR 验证，只有 CIRBP 和 INPP5K mRNA 水平在妇科癌症中同时显着降低，并且与总生存率呈负相关。我们还发现 CIRBP 或 INPP5K DNA 甲基化、AS 和 APA 事件是妇科癌症的预后指标。 T 细胞的激活可能是这些基因调节癌症进展的主要信号通路。 CIRBP/INPP5K 表达与免疫浸润呈正相关，是生存的主要危险因素，特别是在子宫体子宫内膜癌 (UCEC) 患者中。结论 根据这些发现，CIRBP 和 INPP5K 的 DNA 甲基化、AS 和 APA 事件可能通过调节 T 细胞浸润而成为妇科癌症重要的预后生物标志物和靶标。
Background To depict the prognostic landscape of gynecological cancers from the perspective of DNA methylation, alternative splicing (AS) and polyadenylation (APA) events and investigate their correlation with immune infiltrates. Methods Methylation and RNA-seq data and corresponding clinical information regarding gynecologic cancers were used to explore the relationships between changes in DNA methylation, AS and APA events and gynecologic cancer prognosis. QRT-PCR and multiple bioinformatics tools were employed to construct a gene interaction network and explore immune infiltrates. Results Only the mRNA levels of CIRBP and INPP5K were simultaneously significantly decreased in gynecologic cancers and negatively associated with overall survival, which verified by qrt-PCR. We also identified that CIRBP or INPP5K DNA methylation, AS and APA events are prognostic indicators of gynecologic cancers. The activation of T cells might be the main signaling pathway by which these genes modulate cancer progression. CIRBP/INPP5K expression is positively associated with immune infiltration and is a major risk factor of survival, especially among uterine corpus endometrial carcinoma (UCEC) patients. Conclusion According to these findings, the DNA methylation, AS and APA events of CIRBP and INPP5K may serve as important prognostic biomarkers and targets in gynecological cancers by modulating T cell infiltration.