Expression, clinical significance and biological function of CDC7 in osteosarcoma

CHEN Peijun; MAN Yunan; HE Mingwei; LIANG Bumin; HE Maolin

doi:10.16190/j.cnki.45-1211/r.2025.01.008

Journal of Guangxi Medical University > 2025 > 42(1): 56-64. > DOI: 10.16190/j.cnki.45-1211/r.2025.01.008

CHEN Peijun, MAN Yunan, HE Mingwei, LIANG Bumin, HE Maolin. Expression, clinical significance and biological function of CDC7 in osteosarcoma[J]. Journal of Guangxi Medical University, 2025, 42(1): 56-64. DOI: 10.16190/j.cnki.45-1211/r.2025.01.008

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Expression, clinical significance and biological function of CDC7 in osteosarcoma

1.
Department of Spine and Osteopathy, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
2.
Department of Trauma Orthopedic and Hand Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
3.
International Education School of Guangxi Medical University, Nanning 530021, China

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Received Date: September 09, 2024

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Abstract

Abstracts

Objective
To investigate the expression and clinical significance of cell division cycle 7 (CDC7) in osteosarcoma (OS) and its effect on the proliferation, migration and invasion of OS cells.
Methods
The mRNA microarray data from the Gene Expression Omnibus (GEO) database was used to analyze the expression of CDC7 in OS tissues. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to verify the expression of CDC7 mRNA in human osteoblast cell line (hFOB1.19) and OS cell lines (HOS, U-2 OS, MG63). Immunohistochemistry (IHC) was used to detect the expression of CDC7 protein in 39 cases of OS tissues and 8 cases of adjacent normal tissues. The summary receiver operating characteristic (SROC) curve was employed to evaluate the diagnostic efficacy of CDC7 in OS. Kaplan-Meier survival curves were plotted to analyze the impact of CDC7 expression on the prognosis of OS patients. Univariate and multivariate Cox proportional hazards regression models were utilized to analyze risk factors for poor prognosis in OS. CDC7 small interfering RNA (si-CDC7) was used to transfect HOS cells, and cell proliferation was assessed using cell counting kit-8 (CCK-8) and EdU assays, while cell migration and invasion were evaluated using Transwell assays.
Results
Multiple GEO datasets indicated that CDC7 expression was up-regulated in OS (P < 0.05). Compared with hFOB1.19 cells, CDC7 mRNA expression was increased in HOS, U-2 OS and MG63 cells (P < 0.05). CDC7 protein was highly expressed in OS tissues compared with normal tissues (P < 0.001). CDC7 demonstrated good diagnostic potential for OS (AUC=0.73, 95% CI: 0.69-0.77). Patients with high CDC7 expression had a significant lower survival rate than those with low CDC7 expression (P=0.028). High CDC7 expression was an independent risk factor for poor prognosis in OS (HR=2.471, 95% CI: 1.056-5.781, P=0.037). Silencing CDC7 significantly inhibited the proliferation, migration and invasion of HOS cells.
Conclusion
The expression of CDC7 is upregulated in OS, and it promotes the proliferation, migration and invasion of OS cells, which is expected to be a molecular marker for the diagnosis and prognosis of OS.
- osteosarcoma;
- cell division cycle 7;
- molecular marker;
- proliferation;
- migration;
- invasion

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References

[1]	KANSARA M, THOMSON K, PANG P, et al. Infiltrating myeloid cells drive osteosarcoma progression via GRM4 regulation of IL23[J]. Cancer discovery, 2019, 9(11): 1511-1519. doi: 10.1158/2159-8290.CD-19-0154
[2]	GIANFERANTE D M, MIRABELLO L, SAVAGE S A. Germline and somatic genetics of osteosarcoma-connecting aetiology, biology and therapy[J]. Nature reviews endocrinology, 2017, 13(8): 480-491. doi: 10.1038/nrendo.2017.16
[3]	MARKO T A, DIESSNER B J, SPECTOR L G. Prevalence of metastasis at diagnosis of osteosarcoma: an international comparison[J]. Pediatric blood cancer, 2016, 63(6): 1006-1011. doi: 10.1002/pbc.25963
[4]	EATON B R, SCHWARZ R, VATNER R, et al. Osteosarcoma[J]. Pediatric blood cancer, 2021, 68(Suppl 2): e28352.
[5]	LI C, YU X, GUO D, et al. Association between common polymorphisms in ERCC gene and prognosis of osteosarcoma in patients treated with chemotherapy: a metaanalysis[J]. OncoTargets and therapy, 2018, 11: 3495-504. doi: 10.2147/OTT.S158167
[6]	CERSOSIMO F, LONARDI S, BERNARDINI G, et al. Tumor-associated macrophages in osteosarcoma: from mechanisms to therapy[J]. International journal of molecular sciences, 2020, 21(15): 5207. doi: 10.3390/ijms21155207
[7]	MASAI H, ARAI K. Regulation of DNA replication during the cell cycle: roles of Cdc7 kinase and coupling of replication, recombination, and repair in response to replication fork arrest[J]. IUBMB life, 2000, 49(5): 353-364. doi: 10.1080/152165400410191
[8]	CLARKE L E, FOUNTAINE T J, HENNESSY J, et al. Cdc7 expression in melanomas, Spitz tumors and melanocytic nevi[J]. Journal of cutaneous pathology, 2009, 36(4): 433-438. doi: 10.1111/j.1600-0560.2008.01077.x
[9]	WANG Q, ZHENG W. Upregulation of CDC7 associated with cervical cancer incidence and development[J]. BioMed research international, 2021, 2021: 6663367. doi: 10.1155/2021/6663367
[10]	KULKARNI A A, KINGSBURY S R, TUDZAROVA S, et al. Cdc7 kinase is a predictor of survival and a novel therapeutic target in epithelial ovarian carcinoma[J]. Clinical cancer research, 2009, 15(7): 2417-2425. doi: 10.1158/1078-0432.CCR-08-1276
[11]	DATTA A, GHATAK D, DAS S, et al. p53 gain-offunction mutations increase Cdc7-dependent replication initiation[J]. Embo reports, 2017, 18(11): 2030-2050. doi: 10.15252/embr.201643347
[12]	LORENZ S, BAROY T, SUN J, et al. Unscrambling the genomic chaos of osteosarcoma reveals extensive transcript fusion, recurrent rearrangements and frequent novel TP53 aberrations[J]. Oncotarget, 2016, 7(5): 5273-5288. doi: 10.18632/oncotarget.6567
[13]	MATTHEWS H K, BERTOLI C, DE BRUIN R A M. Cell cycle control in cancer[J]. Nature reviews molecular cell biology, 2022, 23(1): 74-88. doi: 10.1038/s41580-021-00404-3
[14]	YAMADA M, MASAI H, BARTEK J. Regulation and roles of Cdc7 kinase under replication stress[J]. Cell cycle, 2014, 13(12): 1859-1866. doi: 10.4161/cc.29251
[15]	BONTE D, LINDVALL C, LIU H, et al. Cdc7-Dbf4 kinase overexpression in multiple cancers and tumor cell lines is correlated with p53 inactivation[J]. Neoplasia, 2008, 10(9): 920-931. doi: 10.1593/neo.08216
[16]	侯芸, 付凯, 王华庆. CDC7 MCM2在弥漫大B细胞淋巴瘤预后和治疗中的作用[J]. 中国肿瘤临床, 2013, 40(11): 678-681.
[17]	LI Q, XIE W, WANG N, et al. CDC7-dependent transcriptional regulation of RAD54L is essential for tumorigenicity and radio-resistance of glioblastoma [J]. Translational oncology, 2018, 11(2): 300-306. doi: 10.1016/j.tranon.2018.01.003
[18]	CAO J X, LU Y. Targeting CDC7 improves sensitivity to chemotherapy of esophageal squamous cell carcinoma [J]. OncoTargets and therapy, 2019, 12: 63-74. http://www.dovepress.com/getfile.php?fileID=47093
[19]	张从义, 崔逸峰, 李宝宝, 等. 细胞分裂周期7蛋白在肝癌组织的表达及其对肝癌细胞增殖和侵袭的影响[J]. 实用肿瘤学杂志, 2020, 34(2): 150-155.

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