Identification of MAD2L1 and BUB1B as Potential Biomarkers Associated with Progression and Prognosis of Ovarian Cancer

Rongrong Tang; Jinfei Tong; Shanliang Shang; Guangxiao Li; Fangying Sun; Xiaojing Guan; Jianhua Yang

doi:10.1007/s10528-024-10817-2

Identification of MAD2L1 and BUB1B as Potential Biomarkers Associated with Progression and Prognosis of Ovarian Cancer

Biochem Genet. 2024 Apr 29. doi: 10.1007/s10528-024-10817-2. Online ahead of print.

Authors

Rongrong Tang^{1

2}, Jinfei Tong^{1

3}, Shanliang Shang¹, Guangxiao Li¹, Fangying Sun^{1

2}, Xiaojing Guan¹, Jianhua Yang^{4

5}

Affiliations

¹ Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310018, Zhejiang, People's Republic of China.
² School of Medicine, ShaoXing University, ShaoXing, Zhejiang, China.
³ Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, Zhejiang, China.
⁴ Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310018, Zhejiang, People's Republic of China. yjh2006@zju.edu.cn.
⁵ Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, Zhejiang, China. yjh2006@zju.edu.cn.

PMID: 38683465
DOI: 10.1007/s10528-024-10817-2

Abstract

Ovarian cancer develops insidiously and is frequently diagnosed at advanced stages. Screening for ovarian cancer is an effective strategy for reducing mortality. This study aimed to investigate the molecular mechanisms underlying the development of ovarian cancer and identify novel tumor biomarkers for the diagnosis and prognosis of ovarian cancer. Three databases containing gene expression profiles specific to serous ovarian cancer (GSE18520, GSE12470, and GSE26712) were acquired. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were analyzed for the differentially expressed gene (DEGs). The protein-protein interaction (PPI) network was constructed using the STRING database. The pivotal genes in the PPI network were screened using the Cytoscape software. Survival curve analysis was performed using a Kaplan-Meier Plotter. The cancer genome atlas and Gene Expression Omnibus databases were used to find the relationship between Hub gene and serous ovarian cancer. PCR and immunohistochemistry were used to detect the expression of Hub gene in serous ovarian cancer tissues and cells. Downstream pathways of the candidate tumor marker genes were predicted using Gene Set Enrichment Analysis. In this study, 252 DEGs were screened for pathway enrichment. 20 Hub genes were identified. Survival analysis suggested that Aurka, Bub1b, Cenpf, Cks1b, Kif20a, Mad2l1, Racgap1, and Ube2c were associated with the survival of patients with serous ovarian cancer. MAD2L1 and BUB1B levels were significantly different in serous ovarian cancer at different stages. Finally, Mad2l1 was found to play a role in the cell cycle, oocyte meiosis, and ubiquitin-mediated proteolysis. Meanwhile, Bub1b may play a role in the cell cycle, ubiquitin-mediated proteolysis, and spliceosome processes. Mad2l1 and Bub1b could be used as markers to predict ovarian carcinogenesis and prognosis, providing candidate targets for the diagnosis and treatment of serous ovarian cancer.

Keywords: Bub1b; Mad2l1; Bioinformatics analysis; Diagnostic markers; Ovarian cancer; Prognosis.

Grants and funding

LY23H160015/the Nature Science Foundation of Zhejiang Province