Dysregulation of KIF14 regulates the cell cycle and predicts poor prognosis in cervical cancer: a study based on integrated approaches.

Li Xiao,Sisi Zhang,Shuirong Zhang,Qingyu Zheng

doi:10.1590/1414-431x2021e11363

Abstract

Cervical cancer (CC) is the most common malignant tumor in females. Although persistent high-risk human papillomavirus (HPV) infection is a leading factor that causes CC, few women with HPV infection develop CC. Therefore, many mechanisms remain to be explored, such as aberrant expression of oncogenes and tumor suppressor genes. To identify promising prognostic factors and interpret the relevant mechanisms of CC, the RNA sequencing profile of CC was downloaded from the Cancer Genome Atlas and the Gene Expression Omnibus databases. The GSE63514 dataset was analyzed, and differentially expressed genes (DEGs) were obtained by weighted coexpression network analysis and the edgeR package in R. Fifty-three shared genes were mainly enriched in nuclear chromosome segregation and DNA replication signaling pathways. Through a protein-protein interaction network and prognosis analysis, the kinesin family member 14 (KIF14) hub gene was extracted from the set of 53 shared genes, which was overexpressed and associated with poor overall survival (OS) and disease-free survival (DFS) of CC patients. Mechanistically, gene set enrichment analysis showed that KIF14 was mainly enriched in the glycolysis/gluconeogenesis signaling pathway and DNA replication signaling pathway, especially in the cell cycle signaling pathway. RT-PCR and the Human Protein Atlas database confirmed that these genes were significantly increased in CC samples. Therefore, our findings indicated the biological function of KIF14 in cervical cancer and provided new ideas for CC diagnosis and therapies.

Highlights

Cervical cancer (CC) is the most common type of malignant tumor in females and has affected a vast number of women in the world, especially in sub-Saharan Africa and Southeastern Asia
Our results suggested that shared upregulated differentially expressed genes (DEGs) played a more important role in CC pathogenesis compared with downregulated DEGs
Ten candidate hub genes were extracted through protein-protein interaction (PPI) network analysis of the set of 53 genes, and they were all upregulated in CC compared with cervical intraepithelial neoplasia (CIN) and normal cervical tissues

Summary

Introduction

Cervical cancer (CC) is the most common type of malignant tumor in females and has affected a vast number of women in the world, especially in sub-Saharan Africa and Southeastern Asia. The incidence and mortality of cervical cancer have declined due to vaccination, screening, and control of precancerous lesions, CC incidence is high in some less economically developed areas, affecting young women (peak 45–49) and advancing to the late stage [1]. Persistent high-risk human papillomavirus (HPV) infection is a leading factor that leads to cervical tumor occurrence [3]; few women infected with HPV eventually develop cervical cancer. Other risk factors have been reported and include immunosuppression, smoking, pregnancy history, and long-term contraception, suggesting that the occurrence of CC is a multifactor, multistep complex process related to the environment and involved in the aberrant expression of oncogenes and tumor suppressor genes [4]. It is necessary and urgent to identify sensitive and specific biomarkers that could predict CC prognosis and serve as a target for CC treatment

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