ASPM, CDC20, DLGAP5, BUB1B, CDCA8, and NCAPG May Serve as Diagnostic and Prognostic Biomarkers in Endometrial Carcinoma

Abstract

Uterine Corpus Endometrial Carcinoma (UCEC), the most common gynecologic malignancy in developed countries, remains to be a major public health problem. Further studies are surely needed to elucidate the tumorigenesis of UCEC. Herein, intersecting 203 differentially expressed genes (DEGs) were identified with the GSE17025, GSE63678, and e Cancer Genome Atlas-UCEC datasets. e Gene Ontology/Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis and protein-protein interaction (PPI) network were performed on those 203 DEGs. Intriguingly, 6 of the top 10 nodes in the PPI network were related to unfavorable prognosis, that is, ASPM, CDC20, DLGAP5, BUB1B, CDCA8, and NCAPG. e mRNA and protein expression levels of the 6 hub genes were elevated in UCEC tissues compared to normal tissues. Higher expression of the 6 hub genes was associated with poor prognostic clinicopathological characteristics. e receiver operating characteristic curve suggested the significant diagnostic ability of the 6 hub genes for UCEC. en, underlying pathogeneses of UCEC including promoter methylation level, TP53 mutation status, genomic genetic variation, and immune cells infiltration were analyzed. e mRNA expression level of the 6 hub genes was also higher in cervical squamous cell carcinoma and endocervical adenocarcinoma, uterine carcinosarcoma, and ovarian serous cystadenocarcinoma tissues than in corresponding normal tissues. In conclusion, ASPM, CDC20, DLGAP5, BUB1B, CDCA8, and NCAPG may be considered diagnostic and prognostic biomarkers in UCEC.

Activation of the Anaphase Promoting Complex Restores Impaired Mitotic Progression and Chemosensitivity in Multiple Drug Resistant Human Breast Cancer

“…While CDC20 may be pro-oncogenic, it is unlikely to act in isolation, as at least 60 of the known 69 human APC substrates are associated with multiple cancer types when they accumulate [20], and are now considered a cancer signature [73,74]. A recent series of papers found that APC substrate-mRNAs, including HURP and CDC20, are elevated in multiple cancers, and are now recognized as a hub or signature gene set predictive of poor prognosis cancer (a subset of references are included here; [75][76][77][78]). These substrate accumulations are also associated with more aggressive cancers; in 182 breast tumor samples tested from high grade TNBC, 58% of the samples stained for G1 markers, yet expressed high levels of APC substrates, a cell cycle point when substrates should instead be degraded and at their nadir levels [28].…”

Identification of prognostic biomarkers of invasive ductal carcinoma by an integrated bioinformatics approach

“…68 ASPM is a centrosomal protein that contributes to mitotic spindle formation, orientation, cytokines, neurogenesis, and brain development. 69,70 During metaphase, ASPM is located at the spindle poles, whereas during interphase, it is found in the nucleus and centrosome. Moreover, the ASPM localization to the midbody during cytokinesis suggests that it participates in abscission.…”

“…72 Typically, ASPM has been extensively associated with autosomal primary microcephaly, a brain disorder characterized by a normal-appearing but small brain and mental retardation. 73 However, in the last decade, this gene has also been implicated in the progression of a variety of malignancies, 71 including glioblastoma, cancers of the prostate, breast, bladder, 74 and epithelial ovarian, 71,73 as well as endometrial, 69 hepatocellular, 75 lung, 76 and papillary renal cell carcinoma. 70 ASMP has been recognized by several authors as a significant prognostic gene in cases of BC.…”