Although the treatment technology of ovarian cancer has made great progress, the total mortality of ovarian cancer is the seventh largest cause of death of gynecological malignant tumors [1, 4]. The main causes of OC death are lack of early detection methods, high metastatic tendency and chemotherapy resistance. Therefore, for better treatment of OC, novel specific therapeutic targets should be identified.
Recently, bioinformatics is developing rapidly and microarray and sequencing data is getting more and more popular, which provide a platform for exploring the general genetic changes of tumor, identifying DEGs, and clarifying the molecular mechanism of tumor diagnosis, treatment and prognosis . Therefore, GSE105437, GSE14407 and GSE18520 were downloaded from the GEO databases, from which 821 DEGs were identified, and GO function and KEGG pathway enrichment analysis showed the DEGs were mainly enriched in some vital pathways and functions, whose abnormalities may cause tumor progression and drug resistance. Activations of gene transcription such as HIF-1, STAT-3, PAX3, c-MYB, TGF-β can promote cancer progression in aspects of immune responses, hematopoiesis, neurogenesis, angiogenesis, cell survival, glucose metabolism and invasion, which can be used as therapeutic targets in OC [24-27]. Tubulin is the important component of microtubules that are an important therapeutic target in tumor cells . Paclitaxel as a tubulin inhibitor is the first-line drug for treating OC, but as many as 80% of patients will eventually relapse and become paclitaxel resistant, which may cause treatment failure and poor prognosis of ovarian cancer [29-32]. Therefore, to find new targets for treatment is imminent. Cell cycle is the basic process of cell division, which is closely related to the orderly expression of related genes, cyclin-dependent kinases (CDKs), cell cycle divisions (CDCs), the tumour suppressor p53 and so on, whose abnormalities contribute to carcinogenesis and tumor progression and drugs target for these can be used to treat various cancer [33, 34]. Wnt signaling pathway can be implicated in OC stemness, carcinogenesis of many OC subtypes by regulating cell growth and apoptosis, and attaches great importance to chemoresistance, which can be targeted for chemo-sensitization in OC [35, 36]. Chen, M.W., et al. reported that the Wnt signaling pathway regulates ovarian cancer cells growth, progression, and migration through interaction with STAT3 and miRNA-92 . P450 are a series of metabolic enzymes that can regulate many processes such as anticancer drugs’ pharmacokinetics. Recent studies have shown that individual forms of P450 play a role in the resistance of anticancer drugs [38, 39]. Downie, D., et al. reported that P450 enzymes are overexpressed in OC and can be markers of prognosis . p53 is a famous tumor suppressor gene, which can regulate the cell cycle and avoid the occurrence of cancer. It is jokingly called "the guardian of genome". Generally, p53 gene mutation happens in more than 50% of cancer patients . Chen, Y.N., et al. reported that microRNA let-7d-5p-HMGA1-p53 signaling pathway rescues OC cell apoptosis and restores chemosensitivity in ovarian cancer . Metabolic reprogramming is a marker of malignancy. There are a lot of metabolic heterogeneity between cancer cells and normal tissues, but almost no metabolic activity is limited in tumors. The metabolic phenotype and metabolic dependence keep changing during the development of cancer from precancerous tissue to local invasion and metastasis [43, 44]. These findings help us better understanding the possible mechanisms in OC development, progression, and therapy.
Furthermore, a PPI network was drawn based on the DEGs, from which 30 hub genes that had the highest interactions in the network were identified. By literature mining, it was identified that many OC-related studies had already well studied CDK1. Therefore, CDC20 was selected for further research as a key gene in OC. Previous studies have suggested that CDC20 could function as tumor oncogene [45-51]. However, there lacks works done to explore CDC20 expression level, protein level and related molecular mechanisms in OC. Initially, we used Oncomine database to verify the CDC20 mRNA expression levels between OC and normal ovary tissues. What’s more, we examined the levels of CDC20 mRNA in normal OC tissues and normal ovarian tissues from patients in our hospital. All results indicated CDC20 expression in normal ovarian tissues was lower than that in OC tissues. Next, we predict gene sets and signaling pathways associated with CDC20 using the expression data of three datasets in GSEA software. CDC20 may function in cell cycle, citrate and TCA cycle, oxidative phosphorylation and ubiquitin mediated proteolysis. As SAC target, and APC/C E3 ubiquitin ligase co-activator involving in metaphase and anaphase transition during mitosis, the significance of CDC20 in cell cycle regulation is obvious . The tricarboxylic acid (TCA) cycle is the final metabolic pathway and also the center of carbohydrate, lipid and amino acid metabolism. Oxidative phosphorylation is accompanied by ATP production in biological oxidation, including two types of phosphorylation: metabolite linked phosphorylation and respiratory chain linked phosphorylation. TCA cycle and oxidative phosphorylation are two main process in cells to produce energy, and metabolic reprogramming causes tumorigenesis. From this aspect, controlling cancer energy metabolism becomes a potential treatment. Besides, APC/CCDC20 as an E3 ubiquitin ligase can also promote substrate ubiquitination and their subsequent degradation by the proteasome, which can regulate metabolic signaling pathways, transcription factors, and metabolic enzymes . These show that CDC20 attaches great importance to OC and can be a specific target to treat OC.
In conclusion, we deduce that CDC20 may be a promising therapeutic target for the treatment of OC. However, continued work will be necessary to define whether CDC20 can produce a marked effect and the exact role and mechanism of it in OC Yet, despite the uncertainty of these mechanism, we believe that CDC20 is an appealing potential therapeutic target for OC patients.