Systematic Analysis of the Clinical Relevance of Cell Division Cycle Associated Family in Endometrial Carcinoma

Wenchao Zhang; Xiaofeng Qiu; Di Sun; Danye Zhang; Yue Qi; Xiao Li; Bingying Liu; Juanjuan Liu; Bei Lin

doi:10.7150/jca.46324

Systematic Analysis of the Clinical Relevance of Cell Division Cycle Associated Family in Endometrial Carcinoma

J Cancer. 2020 Jul 20;11(19):5588-5600. doi: 10.7150/jca.46324. eCollection 2020.

Authors

Wenchao Zhang^{1

2}, Xiaofeng Qiu³, Di Sun^{1

2}, Danye Zhang^{1

2}, Yue Qi^{1

2}, Xiao Li^{1

2}, Bingying Liu^{1

2}, Juanjuan Liu^{1

2}, Bei Lin^{1

2}

Affiliations

¹ Affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Liaoning, China, Post code: 110000.
² Affiliation: Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Liaoning, China, Post code: 110000.
³ Affiliation: Department of Obstetrics and Gynecology, Zaozhuang Shizhong District Maternal and Child Health Hospital, Shandong, China.

Abstract

Background: Endometrial carcinoma (EC) is the most common cancer of female reproductive system, thus requiring for new effective biomarkers which could predict the onset of EC and worse prognosis. Cell Division Cycle Associated (CDCA) family plays indispensable roles in cell cycle process. However, no study has been focused on the role of CDCAs in EC. Our study aims to investigate the clinical relevance, potential biologic functions and molecular mechanisms of CDCAs in EC. Methods: GEPIA, cBioPortal, GeneMANIA, Networkanalyst, TCGA-UCEC cohort were utilized in this study. Results: NUF2 and CDCA2/3/4/5/7/8 were significantly highly expressed in EC compared with normal tissues. The patients with high NUF2 and CDCA2/3/4/5/8 expression tended to develop to advanced FIGO stages, poor differentiation and worse prognosis(in both OS and RFS analyses) than those with low expression. By contrast, elevated CDCA7 was significantly associated with better prognosis. CBX2 exerted no significant prognostic impact on EC patients. Distinct patterns of the genetic alterations of CDCAs were observed in various histological subtypes of EC. The biological functions of NUF2 and CDCA2/3/4/5/8 were mainly related with the activation of the following pathway: cell cycle, DNA replication, base excision repair, mismatch repair, nucleotide excision repair, cellular senescence and p53 signaling pathway. Conclusions: Our study provides new insight into the onset and progression of EC and proposes NUF2 and CDCA2/3/4/5/8 could act as oncogenes and have shown great diagnostic and prognostic promise in improving EC patient detection and survival prediction with accuracy.

Keywords: CDCA; TCGA; endometrial carcinoma; prognosis.