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The role of the CDCA gene family in ovarian cancer.

ABSTRACT: Background:Ovarian cancer is a frequently-occurring reproductive system malignancy in females, which leads to an annual of over 100 thousand deaths worldwide. Methods:The electronic databases, including GEPIA, ONCOMINE, Metascape, and Kaplan-Meier Plotter, were used to examine both survival and transcriptional data regarding the cell division cycle associated (CDCA) gene family among ovarian cancer patients. Results:All CDCA genes expression levels were up-regulated in ovarian cancer tissues relative to those in non-carcinoma ovarian counterparts. Besides, CDCA5/7 expression levels were related to the late tumor stage. In addition, the Kaplan-Meier Plotter database was employed to carry out survival analysis, which suggested that ovarian cancer patients with increased CDCA2/3/5/7 expression levels had poor overall survival (OS) (P<0.05). Moreover, ovarian cancer patients that had up-regulated mRNA expression levels of CDCA2/5/8 had markedly reduced progression-free survival (PFS) (P<0.05); and up-regulated CDCA4 expression showed remarkable association with reduced post-progression survival (PPS) (P<0.05). Additionally, the following processes were affected by CDCA genes alterations, including R-HAS-2500257: resolution of sister chromatid cohesion; GO:0051301: cell division; CORUM: 1118: Chromosomal passenger complex (CPC, including CDCA8, INCENP, AURKB and BIRC5); CORUM: 127: NDC80 kinetochore complex; M129: PID PLK1 pathway; and GO: 0007080: mitotic metaphase plate congression, all of which were subjected to marked regulation since the alterations affected CDCA genes. Conclusions:Up-regulated CDCA gene expression in ovarian cancer tissues probably played a crucial part in the occurrence of ovarian cancer. The up-regulated CDCA2/3/5/7 expression levels were used as the potential prognostic markers to improve the poor ovarian cancer survival and prognostic accuracy. Moreover, CDCA genes probably exerted their functions in tumorigenesis through the PLK1 pathway.

SUBMITTER: Chen C

PROVIDER: S-EPMC7154490 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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The role of the <i>CDCA</i> gene family in ovarian cancer.

Chen Chongxiang C Chen Siliang S Luo Ma M Yan Honghong H Pang Lanlan L Zhu Chaoyang C Tan Weiyan W Zhao Qingyu Q Lai Jielan J Li Huan H

Annals of translational medicine 20200301 5

<h4>Background</h4>Ovarian cancer is a frequently-occurring reproductive system malignancy in females, which leads to an annual of over 100 thousand deaths worldwide.<h4>Methods</h4>The electronic databases, including GEPIA, ONCOMINE, Metascape, and Kaplan-Meier Plotter, were used to examine both survival and transcriptional data regarding the cell division cycle associated (<i>CDCA</i>) gene family among ovarian cancer patients.<h4>Results</h4>All <i>CDCA</i> genes expression levels were up-reg ...[more]

PMID: 32309337

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Project description:ObjectiveBreast cancer susceptibility gene 1/2 (BRCA1/2) is the most important susceptibility gene associated with hereditary ovarian cancer (HOC). We aimed to screen BRAC1 and BRAC2 gene mutations in a member of a hereditary ovarian cancer family in China, and to analyze the structure and function of the mutant protein.MethodsA typical HOC family was selected. Blood samples and pathological tissue samples were taken from the female members of the family. Blood samples from two patients with sporadic ovaries of the same pathological type were taken as a control group. After RNA extraction, PCR amplification was applied and the PCR products were directly sequenced and aligned, prediction and analysis of protein structure and molecular conformation that may be caused by BRCA1/2 mutation.ResultsThe whole gene analysis of BRCA1 and BRCA2 in ovarian cancer patients in the family showed that there were 8 mutations in BRCA1 whole gene sequencing, including 3 nonsense mutations (2314C>T, 2543T>C, 4540T>C); two mutations have been recorded, which are associated with cervical cancer (2844C>T) and endometriosis (3345A>G); three newly discovered mutations (3780A>G, 5069A>G, 3326A>T). Among them, 3780A>G and 5069A>G caused amino acid changes, while 3326A>T mutation caused Arg mutation to stop codon. A total of 7 mutations were detected in BRCA2 whole-genome sequencing, including 5 non-significant mutations (3623A>G, 4034T>C, 4790A>G, 6740G>C, 7469A>G); one no-record mutation (1716T>A), and 1 recorded mutation (1342A>C), which was associated with breast cancer and ovarian cancer. BRCA1 (3326A>T) and BRCA2 (1342A>C) mutations were co-existing in patients (II1, II3, and II5) identified as serous adenocarcinoma grade II. Two cases of ovarian serous cystadenocarcinoma with no history of family tumors were normalized for BRCA1/2 gene sequencing. In the gene detection of III generation female, four females with BRCA2 (1342A>C) mutation were found, and one of them also carried the BRCA1 (3326A>T) mutation, who can be considered a high-risk group of HOC in this family. Online protein structure predictions revealed that BRCA1 (3326A>T) mutations mutated AGA at this site to TGA resulting in a translated Arg (arginine) mutation as a stop codon, while BRCA2 (1342A>C) mutated AAT at this site to CAT resulting in a translated Asn mutation to His.ConclusionThe BRCA1 (3326A>T) and BRCA2 (1342A>C) were detected in the HOC family, which may be the susceptibility gene of the family's HOC. The BRCA1/2 gene screening may be possible to obtain high-risk populations in this family.

Dataset Information

The role of the CDCA gene family in ovarian cancer.

Publications

The role of the <i>CDCA</i> gene family in ovarian cancer.

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