MRPL15 是上皮性卵巢癌的一种新型预后生物标志物和治疗靶点。
MRPL15 is a novel prognostic biomarker and therapeutic target for epithelial ovarian cancer.
机构信息
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Key Laboratory of Maternal-Fetal Medicine of Liaoning Province and Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shenyang, China.
出版信息
Cancer Med. 2021 Jun;10(11):3655-3673. doi: 10.1002/cam4.3907. Epub 2021 May 2.
PURPOSE
To analyze the role of six human epididymis protein 4 (HE4)-related mitochondrial ribosomal proteins (MRPs) in ovarian cancer and selected MRPL15, which is most closely related to the tumorigenesis and prognosis of ovarian cancer, for further analyses.
METHODS
Using STRING database and MCODE plugin in Cytoscape, six MRPs were identified among genes that are upregulated in response to HE4 overexpression in epithelial ovarian cancer cells. The Cancer Genome Atlas (TCGA) ovarian cancer, GTEX, Oncomine, and TISIDB were used to analyze the expression of the six MRPs. The prognostic impact and genetic variation of these six MRPs in ovarian cancer were evaluated using Kaplan-Meier Plotter and cBioPortal, respectively. MRPL15 was selected for immunohistochemistry and GEO verification. TCGA ovarian cancer data, gene set enrichment analysis, and Enrichr were used to explore the mechanism of MRPL15 in ovarian cancer. Finally, the relationship between MRPL15 expression and immune subtype, tumor-infiltrating lymphocytes, and immune regulatory factors was analyzed using TCGA ovarian cancer data and TISIDB.
RESULTS
Six MRPs (MRPL10, MRPL15, MRPL36, MRPL39, MRPS16, and MRPS31) related to HE4 in ovarian cancer were selected. MRPL15 was highly expressed and amplified in ovarian cancer and was related to the poor prognosis of patients. Mechanism analysis indicated that MRPL15 plays a role in ovarian cancer through pathways such as the cell cycle, DNA repair, and mTOR 1 signaling. High expression of MRPL15 in ovarian cancer may be associated with its amplification and hypomethylation. Additionally, MRPL15 showed the lowest expression in C3 ovarian cancer and was correlated with proliferation of CD8 T cells and dendritic cells as well as TGFβR1 and IDO1 expression.
CONCLUSION
MRPL15 may be a prognostic indicator and therapeutic target for ovarian cancer. Because of its close correlation with HE4, this study provides insights into the mechanism of HE4 in ovarian cancer.
目的
分析 6 个人附睾蛋白 4（HE4）相关的线粒体核糖体蛋白（MRP）在卵巢癌中的作用，并选择与卵巢癌的发生和预后最密切相关的 MRPL15 进行进一步分析。
方法
使用 STRING 数据库和 Cytoscape 中的 MCODE 插件，在响应 HE4 过表达的上皮性卵巢癌细胞中鉴定出 6 种上调的 MRP。使用癌症基因组图谱（TCGA）卵巢癌、GTEX、Oncomine 和 TISIDB 分析这 6 种 MRP 的表达。使用 Kaplan-Meier Plotter 和 cBioPortal 分别评估这 6 种 MRP 在卵巢癌中的预后影响和遗传变异。选择 MRPL15 进行免疫组化和 GEO 验证。使用 TCGA 卵巢癌数据、基因集富集分析和 Enrichr 来探索 MRPL15 在卵巢癌中的作用机制。最后，使用 TCGA 卵巢癌数据和 TISIDB 分析 MRPL15 表达与免疫亚型、肿瘤浸润淋巴细胞和免疫调节因子的关系。
结果
选择了与卵巢癌中 HE4 相关的 6 种 MRP（MRPL10、MRPL15、MRPL36、MRPL39、MRPS16 和 MRPS31）。MRPL15 在卵巢癌中高表达和扩增，并与患者的不良预后相关。机制分析表明，MRPL15 通过细胞周期、DNA 修复和 mTOR 1 信号等途径在卵巢癌中发挥作用。卵巢癌中 MRPL15 的高表达可能与其扩增和低甲基化有关。此外，MRPL15 在 C3 卵巢癌中表达最低，与 CD8 T 细胞和树突状细胞的增殖以及 TGFβR1 和 IDO1 的表达相关。
结论
MRPL15 可能是卵巢癌的预后指标和治疗靶点。由于其与 HE4 密切相关，本研究为 HE4 在卵巢癌中的作用机制提供了新的见解。
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