Bioinformatics analysis shows that TOP2A functions as a key candidate gene in the progression of cervical cancer

Abstract

Cervical cancer (CC) is one of the most prevalent types of cancer affecting females worldwide. However, the molecular mechanisms underlying the development and progression of CC remains to be elucidated. Taking the high incidence and mortality rates amongst women into consideration, the identification of novel biomarkers to prevent CC is of great significance and required to improve diagnosis. Using three raw microarray datasets from the Gene Expression Omnibus database, 188 differentially expressed genes (DEGs) were identified. Gene Ontology and pathway analyses were performed on the DEGs. Through protein-protein interaction network construction and module analysis, eight hub genes [cell division cycle 6, cyclin-dependent kinase 1 (CDK1), cell division control protein 45, budding uninhibited by benzimidazoles 1 (BUB1), DNA topoisomerase II α (TOP2A) and minichromosome maintenance complex component 4, CCNB2 and CCNB1] were identified, but only TOP2A was considered a prognostic factor in survival analysis. There were strong positive correlations between TOP2A and BUB1 (P<0.0001, rs= 0.635), CDK1 (P<0.0001, rs= 0.511), centromere protein F (CENPF) (P<0.0001, rs= 0.677), Rac GTPase activating protein 1 (RACGAP1) (P<0.0001, rs= 0.612), F-box protein 5 (FBXO5) (P<0.0001, rs=0.585) and BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) (P<0.0001, rs= 0.584). Additionally, BUB1, CDK1, CENPF, RACGAP1, FBXO5 and BUB1B are all potentially suitable candidate targets for the diagnosis and treatment of CC. In conclusion, the present study identified TOP2A as a potential tumor oncogene and a biomarker for the prognosis of CC.

Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer

“…FBXO5 has been suggested to play crucial roles in the development of HCC, cervical cancer and squamous-cell lung carcinoma in the latest research on bioinformatics analysis [46][47][48]. Also, we got the similar results in BC.…”

Bioinformatics analysis of differentially expressed genes and pathways in the development of cervical cancer

“…There were 83 upregulated genes and 7 downregulated genes in the CIN-CC group. Furthermore, 155 upregulated genes in the N-CC group, including TCAM1P , MCM2 , HS6ST2 , AIM2 , CDKN2A , RFC4 , PLOD2 , APOC1 and CENPF [ 19 ], were shared among the three datasets. Among the 208 downregulated genes, 51 were shared among the three datasets: TMPRSS11B , BBOX1 , ZSCAN18 , ENDOU , KLK8 , ANKRD35 , A2ML1 , CRYAB , MAL , VSIG10L , ECM1 , SPINK5 , TM7SF2 , SPINK7 , PRSS27 , RBP7 , PRSS3 , ACPP , HPGD , CWH43 , RHCG , SCEL , TP53I3 , SPRR2C , CRABP2 , HCG22 , DMKN , PRSS2 , CLIC3 , SPNS2 , LCE3D , FUT3 , RDH12 , CRNN , CEACAM7 , LYNX1 , MYZAP , KRTDAP , NDRG4 , SLC5A1 , GPX3 , PPP1R3C , SLURP1 , SLC24A3 , THSD4 , PSCA , CDA , FAM3D , CFD , HOPX , and CRCT1 .…”

“…Critical subnetworks might strongly contribute to the occurrence and development of cervical cancer and have high diagnostic value. Further analysis showed that NUSAP1 [ 36 ] , TOP2A, KIF2C [ 37 ] , NDC80 [ 23 ] , ASPM [ 21 , 38 ] , KIF20A [ 39 ] , CDK1 [ 19 , 38 ] , KIF11 [ 40 , 41 ] , BIRC5 [ 42 ] , MCM2 and CHEK1 [ 40 , 41 , 43 ] were high scoring hub genes and showed significantly upregulated expression in cervical cancer tissues compared with normal tissues ( P < 0.01). By analyzing the prognostic values of the hub genes from the 12 subnetworks, a total of 14 potential molecular targets ( MCM2 [ 23 , 35 , 44 – 46 ], TOP2A [ 19 , 35 , 40 ], BLM, RMI2 , EXO1 , RFC4 , PSCA , KNTC1 , CDC45 , GINS2 , CXCL8 , TNFAIP6 , CXCL5 , and CDA ) were obtained and annotated.…”

Identification of Core Genes Involved in the Progression of Cervical Cancer Using an Integrative mRNA Analysis

“…Previous studies have described an abnormal regulation of the cell cycle mechanism that plays a vital role in both tumorigenesis and progression, including that detected in CC [ 26 ]. In this study, a more complex alteration mechanism at both mRNA and miRNA is observed.…”