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

Shaochong Lin,1,2 Junpeng Du,3 Jun Hao,1 Xiaohua Luo,1 Han Wu,1 Huifang Zhang,1 Xinxin Zhao,1 Lida Xu,1 BaoJin Wang1,2 1Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Henan International Joint Laboratory of Ovarian Malignant Tumor, Zhengzhou, 450052, People’s Republic of China; 3Department of Pediatric Surgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of ChinaCorrespondence: BaoJin WangDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, No. 7, Kangfu Front Street, Erqi District, Zhengzhou, 450052, People’s Republic of ChinaTel +86 156 3927 7692Fax +86 371-66903480Email 2995269936@qq.comPurpose: 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