Significant Value of XRCC2 and XRCC9 Expression in the Prognosis of Human Ovarian Carcinoma

Overview

Journal J Cancer

Specialty Oncology

Date 2021 Sep 20

PMID 34539898

Citations 6

Authors

Yi Liu

Yichi Xu

Mengying Jiang

Weinan Chen

Xueqiong Zhu

Affiliations

Soon will be listed here.

Abstract

The x-ray repair cross-complementing (XRCC) family is essential in DNA repair processes. The predictive roles of XRCCs remain unclear in ovarian carcinomas. Therefore, detecting the relationship between XRCCs expression and ovarian carcinomas prognosis is increasingly pivotal. Using the "Kaplan-Meier (KM) plotter" database, progression-free survival (PFS) and overall survival (OS) were utilized to evaluate the prognosis of XRCCs mRNA expression in ovarian carcinoma patients with clinical outcomes. Then, mRNA level and protein levels of XRCCs were assessed in normal ovarian cells and ovarian carcinoma cell lines by real-time qPCR, Western blotting and immunofluorescence analysis. Additionally, expression of the XRCCs protein in tissues from ovarian carcinomas and normal ovary was identified by immunohistochemical staining. Higher mRNA levels of XRCC2 and XRCC9 predicted longer PFS and OS in all women with ovarian malignance, while elevated XRCC4 mRNA levels were linked to poor PFS and OS in all ovarian cancer patients. Elevated mRNA of XRCC2 was also correlated with better PFS in patients with serous ovarian carcinomas, and better PFS and OS in grade III and stage III+IV ovarian carcinomas patients. What's more, highly expressed levels of XRCC9 mRNA were also linked to favorable PFS and OS in patients with serous, grade III and stage III+IV ovarian carcinomas. Nevertheless, elevated mRNA expression of XRCC4 was linked to worse PFS and OS for patients with serous, grade III as well as all stages of ovarian malignance. Additionally, when compared to ovarian carcinoma cell lines, elevated mRNA and protein levels of XRCC2 and XRCC9 were detected in normal ovarian cells. Consistently, higher staining of XRCC2 and XRCC9 was also detected in normal ovarian cells than that in ovarian cancer cells. Then, higher staining levels of XRCC2 and XRCC9 were discovered in healthy control tissues than that in ovarian carcinoma tissues. Meanwhile, XRCC4 was identified to be overexpressed in tissues of ovarian malignance as compared to normal control tissues. However, XRCC4 mRNA and protein levels were lower in ovarian cancer cells than that in normal cell line. Elevated XRCC2 and XRCC9 expression levels were observed in normal ovarian cells and tissues than that in ovarian malignance cells and tissues, and exhibited better prognostic value especially in patients with serous, poor differentiated and late stage, suggesting that XRCC2 and XRCC9 may be potent prognostic markers in ovarian cancer patients and can guide personalized surveillance for ovarian malignance.

Citing Articles

Molecular mechanisms of cisplatin resistance in ovarian cancer.

Jiang C, Shen C, Ni M, Huang L, Hu H, Dai Q Genes Dis. 2024; 11(6):101063.

PMID: 39224110 PMC: 11367050. DOI: 10.1016/j.gendis.2023.06.032.

Methylation of BRD4 by PRMT1 regulates BRD4 phosphorylation and promotes ovarian cancer invasion.

Liu Y, Liu H, Ye M, Jiang M, Chen X, Song G Cell Death Dis. 2023; 14(9):624.

PMID: 37737256 PMC: 10517134. DOI: 10.1038/s41419-023-06149-5.

PRAME Promotes Cervical Cancer Proliferation and Migration via Wnt/β-Catenin Pathway Regulation.

Chen X, Jiang M, Zhou S, Chen H, Song G, Wu Y Cancers (Basel). 2023; 15(6).

PMID: 36980687 PMC: 10046627. DOI: 10.3390/cancers15061801.

Response of the Urothelial Carcinoma Cell Lines to Cisplatin.

Holickova A, Roska J, Orasova E, Bruderova V, Palacka P, Jurkovicova D Int J Mol Sci. 2022; 23(20).

PMID: 36293346 PMC: 9604399. DOI: 10.3390/ijms232012488.

XRCC2 reduced the sensitivity of NSCLC to radio-chemotherapy by arresting the cell cycle.

Shan J, Wang X, Zhao J Am J Transl Res. 2022; 14(6):3783-3795.

PMID: 35836870 PMC: 9274602.

References

Kang Y, Balter B, Csizmadia E, Haas B, Sharma H, Bronson R . Contribution of classical end-joining to PTEN inactivation in p53-mediated glioblastoma formation and drug-resistant survival. Nat Commun. 2017; 8:14013. PMC: 5247582. DOI: 10.1038/ncomms14013. View

Vergote I, Trope C, Amant F, Kristensen G, Ehlen T, Johnson N . Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010; 363(10):943-53. DOI: 10.1056/NEJMoa0908806. View

Yuan C, Liu X, Li R, Yan S, Kong B . Analysis of the association between the XRCC2 rs3218536 polymorphism and ovarian cancer risk. Arch Med Sci. 2020; 16(3):682-691. PMC: 7212224. DOI: 10.5114/aoms.2020.94657. View

Yoon M, Cha H, Ahn J, Lee D, Jeong H, Koo H . Dysfunctional activity of classical DNA end-joining renders acquired resistance to carboplatin in human ovarian cancer cells. Cancer Lett. 2021; 520:267-280. DOI: 10.1016/j.canlet.2021.08.003. View

Andrew A, Gui J, Hu T, Wyszynski A, Marsit C, Kelsey K . Genetic polymorphisms modify bladder cancer recurrence and survival in a USA population-based prognostic study. BJU Int. 2014; 115(2):238-47. PMC: 4533837. DOI: 10.1111/bju.12641. View

Zienolddiny S, Campa D, Lind H, Ryberg D, Skaug V, Stangeland L . Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis. 2005; 27(3):560-7. DOI: 10.1093/carcin/bgi232. View

Stewart S, Harewood R, Matz M, Rim S, Sabatino S, Ward K . Disparities in ovarian cancer survival in the United States (2001-2009): Findings from the CONCORD-2 study. Cancer. 2017; 123 Suppl 24:5138-5159. PMC: 5785937. DOI: 10.1002/cncr.31027. View

Putthanachote N, Promthet S, Hurst C, Suwanrungruang K, Chopjitt P, Wiangnon S . The XRCC 1 DNA repair gene modifies the environmental risk of stomach cancer: a hospital-based matched case-control study. BMC Cancer. 2017; 17(1):680. PMC: 5637079. DOI: 10.1186/s12885-017-3675-9. View

Kamali M, Hamadani S, Neamatzadeh H, Mazaheri M, Shehneh M, Modaress Gilani M . Association of XRCC2 rs3218536 Polymorphism with Susceptibility of Breast and Ovarian Cancer: A Systematic Review and Meta-Analysis. Asian Pac J Cancer Prev. 2017; 18(7):1743-1749. PMC: 5648374. DOI: 10.22034/APJCP.2017.18.7.1743. View

10.

Zheng Z, Wang P, Wang H, Zhang X, Wang M, Cucinotta F . Combining heavy ion radiation and artificial microRNAs to target the homologous recombination repair gene efficiently kills human tumor cells. Int J Radiat Oncol Biol Phys. 2012; 85(2):466-71. DOI: 10.1016/j.ijrobp.2012.04.008. View

11.

Zhang Y, An J, Liu Y, Wu X, Han S, Ren X . XRCC2-Deficient Cells are Highly Sensitive to 5-Fluorouracil in Colorectal Cancer. Cell Physiol Biochem. 2017; 43(3):1207-1219. DOI: 10.1159/000481762. View

12.

Nishikawa T, Munshi A, Story M, Ismail S, Stevens C, Chada S . Adenoviral-mediated mda-7 expression suppresses DNA repair capacity and radiosensitizes non-small-cell lung cancer cells. Oncogene. 2004; 23(42):7125-31. DOI: 10.1038/sj.onc.1207917. View

13.

He Y, Zhang Y, Jin C, Deng X, Wei M, Wu Q . Impact of XRCC2 Arg188His polymorphism on cancer susceptibility: a meta-analysis. PLoS One. 2014; 9(3):e91202. PMC: 3951328. DOI: 10.1371/journal.pone.0091202. View

14.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

15.

Willis S, Villalobos V, Gevaert O, Abramovitz M, Williams C, Sikic B . Single Gene Prognostic Biomarkers in Ovarian Cancer: A Meta-Analysis. PLoS One. 2016; 11(2):e0149183. PMC: 4757072. DOI: 10.1371/journal.pone.0149183. View

16.

Gyorffy B, Lanczky A, Eklund A, Denkert C, Budczies J, Li Q . An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients. Breast Cancer Res Treat. 2009; 123(3):725-31. DOI: 10.1007/s10549-009-0674-9. View

17.

Griffin C, Simpson P, Wilson C, Thacker J . Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation. Nat Cell Biol. 2000; 2(10):757-61. DOI: 10.1038/35036399. View

18.

Siegel R, Miller K, Fuchs H, Jemal A . Cancer Statistics, 2021. CA Cancer J Clin. 2021; 71(1):7-33. DOI: 10.3322/caac.21654. View

19.

Decker B, Allen J, Luccarini C, Pooley K, Shah M, Bolla M . Rare, protein-truncating variants in , and , but not , are associated with increased breast cancer risks. J Med Genet. 2017; 54(11):732-741. PMC: 5740532. DOI: 10.1136/jmedgenet-2017-104588. View

20.

Gyorffy B, Lanczky A, Szallasi Z . Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients. Endocr Relat Cancer. 2012; 19(2):197-208. DOI: 10.1530/ERC-11-0329. View