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Expression of Nuclear Division Cycle 80 Complex Genes in Ovarian Cancer and Correlation with the Clinicopathological Features and Survival Outcomes

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Indian Journal of Gynecologic Oncology Aims and scope Submit manuscript

Abstract

Purpose

Aberrant expression of the nuclear division cycle 80 (NDC80) complex has been implicated in various cancers but remains understudied in ovarian cancer (OC). This study aimed to evaluate the mRNA expression of NDC80 complex genes (NDC80, NUF2, SPC24, and SPC25) in OC and explore possible associations with the clinicopathological features of OC patients.

Methods

NDC80, NUF2, SPC24, and SPC25 mRNA expression levels were evaluated in 40 OC tissue specimens and 40 adjacent non-cancerous ovarian tissue specimens by real-time quantitative PCR. Correlations of the genes’ expression with the patients’ clinicopathological data were reviewed. Effect of the genes’ expression on survival outcomes was assessed using Kaplan–Meier plotter. Logistic regression analysis was used to identify predictors of higher tumor stages among OC patients.

Results

All four genes were significantly overexpressed in OC tissues compared to adjacent non-cancerous ovarian tissues. NDC80, SPC24, and SPC25 demonstrated significant diagnostic values. Combinations of NDC80 + SPC24, NUF2 + SPC24, and SPC24 + SPC25 showed a diagnostic advantage over single-gene analysis. NDC80 and NUF2 were associated with late tumor stages. NUF2 was associated with bilateral ovarian masses. SPC24 was related to negative PR status. The mRNA expression of NDC80, NUF2, and SPC25 was positively correlated. NUF2 overexpression and mutated p53 were significant predictors of higher tumor stages. NDC80, NUF2, and SPC25 predicted poor overall survival. NDC80 and NUF2 predicted poor progression-free survival.

Conclusion

Overexpression of NDC80 complex genes is involved in OC pathogenesis. The genes may serve as potential biomarkers for OC diagnosis and prognosis.

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Abbreviations

AUC:

Area under the ROC curve

BMI:

Body mass index

CA125:

Cancer antigen 125

cDNA:

Complementary DNA

CIN:

Chromosome instability

EOC:

Epithelial ovarian cancer

ER:

Estrogen receptor

FIGO:

International Federation of Gynecology and Obstetrics

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GEO:

Gene Expression Omnibus

HGSC:

High-grade serous carcinoma

KM:

Kaplan–Meier

MAPK:

Mitogen-activated protein kinase

Mdm 2:

Mouse double minute 2

NCBI:

National Center for Biotechnology Information

NDC80:

Nuclear division cycle 80

OC:

Ovarian cancer

OS:

Overall survival

PFS:

Progression-free survival

PI3K-AKT:

Phosphatidylinositol 3-kinase-AKT serine/threonine kinase

PR:

Progesterone receptor

ROC:

Receiver operating characteristic

RT-qPCR:

Real-time quantitative polymerase chain reaction

TCGA:

The Cancer Genome Atlas

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Acknowledgements

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Funding

The authors declare that no funding was received for conducting this study.

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Authors and Affiliations

  1. Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Mai A. Nasser, Hanaa M. Abdeen, Mustafa Neamatallah & Hoda Ahmed Nada

  2. Oncology Center, Mansoura University (OCMU), Mansoura, Egypt

    Basel Refky & Mahmoud Adel Abd Elghaffar

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Contributions

HAN, MN, HMA, and BR contributed to the study conception and design. BR and MAA contributed to specimen and data collection. MAN performed the experiments. HAN, MN, HMA, BR, and MAN analyzed the experiment results. MAN wrote the first draft of the manuscript. HAN, MN, HMA, and BR revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mai A. Nasser.

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Conflict of Interest

The authors have no relevant financial or non-financial interests to disclose.

Data Availability

All data analyzed during this study are included in this article and its supplementary information files.

Ethics Approval

This case–control study was performed in line with the Declaration of Helsinki. The study’s protocol gained approval from the “Institutional Review Board (IRB)” of the Faculty of Medicine, Mansoura University, Egypt (code number: MDP.20.11.48).

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Written informed consent was obtained from all participants.

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Supplementary Information

Below is the link to the electronic supplementary material.

40944_2024_853_MOESM1_ESM.docx

Supplementary file1 (DOCX 14 KB) Supplementary Table 1 ROC curve analysis of NDC80, NUF2, SPC24, and SPC25 in ovarian cancer diagnosis.

40944_2024_853_MOESM2_ESM.docx

Supplementary file2 (DOCX 14 KB) Supplementary Table 2 ROC curve analysis of NDC80 complex genes (two-gene combinations) in ovarian cancer diagnosis.

40944_2024_853_MOESM3_ESM.docx

Supplementary file3 (DOCX 21 KB) Supplementary Table 3 Association between the mRNA expression of NDC80 complex genes and clinicopathological parameters of the studied OC patients.

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Nasser, M.A., Refky, B., Abdeen, H.M. et al. Expression of Nuclear Division Cycle 80 Complex Genes in Ovarian Cancer and Correlation with the Clinicopathological Features and Survival Outcomes. Indian J Gynecol Oncolog 22, 68 (2024). https://doi.org/10.1007/s40944-024-00853-6

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