Identifying Mitotic Kinesins As Potential Prognostic Biomarkers in Ovarian Cancer Using Bioinformatic Analyses

Overview

Journal Diagnostics (Basel)

Specialty Radiology

Date 2022 Feb 25

PMID 35204562

Authors

Hailun Liu

Chen Chen

Tanja Fehm

Zhongping Cheng

Hans Neubauer

Affiliations

Soon will be listed here.

Abstract

Ovarian cancer (OC) is characterized by late-stage presentation, chemoresistance, and poor survival. Evaluating the prognosis of OC patients via effective biomarkers is essential to manage OC progression and to improve survival; however, it has been barely established. Here, we intend to identify differentially expressed genes (DEGs) as potential prognostic biomarkers of OC via bioinformatic analyses. Initially, a total of thirteen DEGs were extracted from different public databases as candidates. The expression of KIF20A, one of the DEGs, was correlated with a worse outcome of OC patients. The functional correlation of the DEGs with mitosis and the prognostic value of KIF20A imply a high correlation between mitotic kinesins (KIFs) and OC development. Finally, we found that KIF20A, together with the other nine mitotic KIFs (4A, 11, 14, 15, 18A, 18B, 23, C1, and2C) were upregulated and activated in OC tissues. Among the ten, seven overexpressed mitotic KIFs (11, 14, 18B, 20A, 23, and C1) were correlated with unfavorable clinical prognosis. Moreover, KIF20A and KIF23 overexpression was associated with worse prognosis in OC patients treated with platinum/taxol chemotherapy, while OCs overexpressing mitotic KIFs (11, 15, 18B, and C1) were resistant to MAPK pathway inhibitors. In conclusion, worse outcomes of OC patients were correlated with overexpression of several mitotic KIFs, which may serve both as prognostic biomarkers and therapeutic targets for OC.

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References

Zhang L, Conejo-Garcia J, Katsaros D, Gimotty P, Massobrio M, Regnani G . Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003; 348(3):203-13. DOI: 10.1056/NEJMoa020177. View

Miki H, Setou M, Kaneshiro K, Hirokawa N . All kinesin superfamily protein, KIF, genes in mouse and human. Proc Natl Acad Sci U S A. 2001; 98(13):7004-11. PMC: 34614. DOI: 10.1073/pnas.111145398. View

Li H, Zhang W, Sun X, Chen J, Li Y, Niu C . Overexpression of kinesin family member 20A is associated with unfavorable clinical outcome and tumor progression in epithelial ovarian cancer. Cancer Manag Res. 2018; 10:3433-3450. PMC: 6140728. DOI: 10.2147/CMAR.S169214. View

Patch A, Christie E, Etemadmoghadam D, Garsed D, George J, Fereday S . Whole-genome characterization of chemoresistant ovarian cancer. Nature. 2015; 521(7553):489-94. DOI: 10.1038/nature14410. View

Zheng F, Zhang Y, Chen S, Weng X, Rao Y, Fang H . Mechanism and current progress of Poly ADP-ribose polymerase (PARP) inhibitors in the treatment of ovarian cancer. Biomed Pharmacother. 2020; 123:109661. DOI: 10.1016/j.biopha.2019.109661. View

Liang Y, Yang W . Kinesins in MAPK cascade: How kinesin motors are involved in the MAPK pathway?. Gene. 2018; 684:1-9. DOI: 10.1016/j.gene.2018.10.042. View

Qiu H, Deng S, Li C, Tian Z, Song X, Yao G . High expression of KIF14 is associated with poor prognosis in patients with epithelial ovarian cancer. Eur Rev Med Pharmacol Sci. 2017; 21(2):239-245. View

Chan K, Ozcelik H, Cheung A, Ngan H, Khoo U . Epigenetic factors controlling the BRCA1 and BRCA2 genes in sporadic ovarian cancer. Cancer Res. 2002; 62(14):4151-6. View

Tischer J, Gergely F . Anti-mitotic therapies in cancer. J Cell Biol. 2018; 218(1):10-11. PMC: 6314557. DOI: 10.1083/jcb.201808077. View

10.

Li X, Shu K, Wang Z, Ding D . Prognostic significance of KIF2A and KIF20A expression in human cancer: A systematic review and meta-analysis. Medicine (Baltimore). 2019; 98(46):e18040. PMC: 6867763. DOI: 10.1097/MD.0000000000018040. View

11.

Agarwal R, Kaye S . Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer. 2003; 3(7):502-16. DOI: 10.1038/nrc1123. View

12.

Allen A, Carville S, McKenna F . Diagnosis and management of rheumatoid arthritis in adults: summary of updated NICE guidance. BMJ. 2018; 362:k3015. DOI: 10.1136/bmj.k3015. View

13.

Malumbres M, Barbacid M . Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009; 9(3):153-66. DOI: 10.1038/nrc2602. View

14.

Uhlen M, Fagerberg L, Hallstrom B, Lindskog C, Oksvold P, Mardinoglu A . Proteomics. Tissue-based map of the human proteome. Science. 2015; 347(6220):1260419. DOI: 10.1126/science.1260419. View

15.

Pawar S, Donthamsetty S, Pannu V, Rida P, Ogden A, Bowen N . KIFCI, a novel putative prognostic biomarker for ovarian adenocarcinomas: delineating protein interaction networks and signaling circuitries. J Ovarian Res. 2014; 7:53. PMC: 4098650. DOI: 10.1186/1757-2215-7-53. View

16.

Jain S, Annett S, Morgan M, Robson T . The Cancer Stem Cell Niche in Ovarian Cancer and Its Impact on Immune Surveillance. Int J Mol Sci. 2021; 22(8). PMC: 8071330. DOI: 10.3390/ijms22084091. View

17.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

18.

Fan C, Reader J, Roque D . Review of Immune Therapies Targeting Ovarian Cancer. Curr Treat Options Oncol. 2018; 19(12):74. DOI: 10.1007/s11864-018-0584-3. View

19.

Lheureux S, Gourley C, Vergote I, Oza A . Epithelial ovarian cancer. Lancet. 2019; 393(10177):1240-1253. DOI: 10.1016/S0140-6736(18)32552-2. View

20.

Lagana A, Colonese F, Colonese E, Sofo V, Salmeri F, Granese R . Cytogenetic analysis of epithelial ovarian cancer's stem cells: an overview on new diagnostic and therapeutic perspectives. Eur J Gynaecol Oncol. 2015; 36(5):495-505. View