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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 FAM83 家族基因中的预后生物标志物
Authors Lin S, Du J, Hao J, Luo X, Wu H, Zhang H, Zhao X, Xu L, Wang B
Received 13 July 2021
Accepted for publication 23 October 2021
Published 15 November 2021 Volume 2021:13 Pages 8611—8627
DOI https://doi.org/10.2147/CMAR.S328851
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr A. Emre Eşkazan
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 FAM83 genes in ovarian cancer (OC) have not yet been investigated. This study aimed to explore the clinical significance and prognostic value of FAM83 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 FAM83 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 FAM83H .
Results: Several datasets demonstrated the mRNA levels of FAM83A/D/E/F/H were significantly higher in OC compared with that in normal tissue. Moreover, the upregulation of FAM83D/H has been mutually confirmed in the Oncomine and GEPIA datasets. Kaplan–Meier survival analysis indicated that the FAM83D/H 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 FAM83 genes might affect the survival outcomes of patients with OC. Furthermore, KEGG analysis suggested that FAM83D/H 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 FAM83H 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 FAM83 genes in OC and identified that FAM83D/H might be potential targets for the prognostic monitoring and targeted therapy of OC.
Keywords: FAM83s , ovarian cancer, prognosis, immunohistochemistry, biomarker