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通过生物信息学分析和实验验证鉴定人类卵巢癌中FAM83家族基因的预后生物标志物

Identification of Prognostic Biomarkers Among FAM83 Family Genes in Human Ovarian Cancer Through Bioinformatic Analysis and Experimental Verification.

作者信息

Lin Shaochong, Du Junpeng, Hao Jun, Luo Xiaohua, Wu Han, Zhang Huifang, Zhao Xinxin, Xu Lida, Wang BaoJin

机构信息

Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.

Henan International Joint Laboratory of Ovarian Malignant Tumor, Zhengzhou, 450052, People's Republic of China.

出版信息

Cancer Manag Res. 2021 Nov 15;13:8611-8627. doi: 10.2147/CMAR.S328851. eCollection 2021.

DOI:10.2147/CMAR.S328851
PMID:34815715
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8604648/
Abstract

PURPOSE

Family with sequence similarity 83 (FAM83) is a newly discovered oncogene family, and the members of which can affect the prognosis of patients with malignant tumors via various mechanisms. However, the functions and molecular mechanisms of genes in ovarian cancer (OC) have not yet been investigated. This study aimed to explore the clinical significance and prognostic value of genes in OC.

MATERIALS AND METHODS

We used a series of bioinformatics databases (Oncomine, GEPIA, cBioPortal, Kaplan-Meier plotter, DAVID and TIMER) to investigate the expression status, prognostic value, genetic alteration and biological function of all eight genes in OC. In addition, a tissue microarray cohort (TMA) comprising 99 ovarian tumor tissues and 19 normal ovarian tissues was used to validate the protein expression and clinicopathological significance of .

RESULTS

Several datasets demonstrated the mRNA levels of were significantly higher in OC compared with that in normal tissue. Moreover, the upregulation of has been mutually confirmed in the Oncomine and GEPIA datasets. Kaplan-Meier survival analysis indicated that the upregulation could predict poor prognosis of OC patients who had shorter overall survival (OS) and progression-free survival (PFS). In addition, cBioportal analysis indicated that the genetic alterations of genes might affect the survival outcomes of patients with OC. Furthermore, KEGG analysis suggested that are involved in the progression of OC through the cell cycle signaling pathway, and they had significant co-expression relationship with cell cycle-related genes. Finally, immunohistochemistry analysis confirmed the high expression of protein in OC tissue, suggesting that its expression is positively correlated with the FIGO stage and pathological subtype of OC.

CONCLUSION

This study elucidated the expression status and prognostic value of genes in OC and identified that might be potential targets for the prognostic monitoring and targeted therapy of OC.

摘要

目的

序列相似性家族83(FAM83)是一个新发现的癌基因家族,其成员可通过多种机制影响恶性肿瘤患者的预后。然而,该基因在卵巢癌(OC)中的功能及分子机制尚未见研究报道。本研究旨在探讨该基因在OC中的临床意义及预后价值。

材料与方法

我们利用一系列生物信息学数据库(Oncomine、GEPIA、cBioPortal、Kaplan-Meier plotter、DAVID和TIMER)研究了OC中所有8个该基因的表达状态、预后价值、基因改变及生物学功能。此外,还使用了一个包含99个卵巢肿瘤组织和19个正常卵巢组织的组织芯片队列(TMA)来验证该基因的蛋白表达及临床病理意义。

结果

多个数据集显示,OC中该基因的mRNA水平显著高于正常组织。此外,Oncomine和GEPIA数据集中均相互证实了该基因的上调。Kaplan-Meier生存分析表明,该基因上调可预测OC患者预后不良,其总生存期(OS)和无进展生存期(PFS)较短。此外,cBioportal分析表明,该基因的改变可能影响OC患者的生存结局。此外,KEGG分析提示,该基因通过细胞周期信号通路参与OC进展,且与细胞周期相关基因存在显著共表达关系。最后,免疫组化分析证实OC组织中该蛋白高表达,提示其表达与OC的FIGO分期和病理亚型呈正相关。

结论

本研究阐明OC中该基因的表达状态及预后价值,并确定该基因可能是OC预后监测和靶向治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aec5/8604648/ee9b306d7517/CMAR-13-8611-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aec5/8604648/beff8b34284b/CMAR-13-8611-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aec5/8604648/ee9b306d7517/CMAR-13-8611-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aec5/8604648/beff8b34284b/CMAR-13-8611-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aec5/8604648/ee9b306d7517/CMAR-13-8611-g0003.jpg

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Biochem Biophys Res Commun. 2021 Aug 27;567:63-71. doi: 10.1016/j.bbrc.2021.05.081. Epub 2021 Jun 15.
2
FAM83B inhibits ovarian cancer cisplatin resistance through inhibiting Wnt pathway.FAM83B通过抑制Wnt信号通路来抑制卵巢癌顺铂耐药。
Oncogenesis. 2021 Jan 9;10(1):6. doi: 10.1038/s41389-020-00301-y.
3
Systematic Analysis of Expression Profiles and Prognostic Significance for Family in Non-small-Cell Lung Cancer.
FAM83D 上的 FBXW7 结合位点是癌症治疗的潜在靶点。
Breast Cancer Res. 2024 Mar 7;26(1):37. doi: 10.1186/s13058-024-01795-9.
4
FAM83H Expression Is Associated with Tumor-Infiltrating PD1-Positive Lymphocytes and Predicts the Survival of Breast Carcinoma Patients.FAM83H表达与肿瘤浸润性PD1阳性淋巴细胞相关,并可预测乳腺癌患者的生存情况。
Diagnostics (Basel). 2023 Sep 15;13(18):2959. doi: 10.3390/diagnostics13182959.
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Involvement of FAM83 Family Proteins in the Development of Solid Tumors: An Update Review.FAM83家族蛋白在实体瘤发生发展中的作用:最新综述
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Pan-cancer analysis of the FAM83 family and its association with prognosis and tumor microenvironment.FAM83家族的泛癌分析及其与预后和肿瘤微环境的关联
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