Document Type : Original Article(s)
Authors
- Asmaa Hussein Mohamed 1
- Ola A. Harb 1
- Rehab Hemeda 2
- Mahmoud Sharafedeen 3
- Waleed A. Abd-Elhady 4
- Ramadan M. Ali 4
1 Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt
3 Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt
4 Department of General Surgery, Faculty of Medicine, Zagazig University, Zagazig, Egypt
Abstract
Background: Kinesin family member 23 (KIF23) has an important role in mitosis of cytoplasmic separation process. Casitas B-lineage lymphoma (c-Cbl) is a protein ligase E3 ubiquitin in tyrosine kinase pathways, involved in numerous cell types.
The current study aimed to evaluate the tissue expression of KIF23 and c-Cbl in gastric cancer (GC) tissues and normal gastric mucosa using immunohistochemistry and to investigate the correlation among their expressions, clinicopathological parameters, and the prognosis of patients in order to detect their role in the progression of GC and patientsi prognosis.
Method: We conducted this prospective study on 120 samples retrieved from 120 patients; 80 samples were taken from GC patients and 40 from normal gastric mucosa. We assed tissue protein expression of KIF23 and c-Cbl using immunohistochemistry. We evaluated the correlations between KIF23 and C-Cbl expression with clinicopathological and prognostic parameters of patients.
Results: KIF23 expression level in GC tissues was positively correlated with high pTNM stage (P = 0.001), larger tumor size (P = 0.010), high tumor grade (P = 0.006), poor overall survival (P < 0.001), disease-free survival rates (P = 0.003), and tumor recurrence after therapy (P = 0.004). c-Cbl expression level in GC tissues was positively correlated with early pTNM stage (P = 0.003), lower tumor grade (P = 0.005), the absence of lymph node metastasis (P = 0.023), good response to therapy (P = 0.002), and the absence of tumor recurrence after the therapy (P = 0.004).
Conclusion: The high KIF23 expression and low c-Cbl expression in GC tissues were attributed to progression and poor prognosis in gastric cancer patients.
Keywords
How to cite this article:
Mohamed AH, Harb OA, Hemeda R, Sharafedeen M, Abd-Elhady WA, Ali RM. Prognostic performance of high expression of KIF23 and loss of c-CBL in gastric cancer patients: An immunohistochemical study. Middle East J Cancer. 2022;13(3):393-403. doi: 10.30476/mejc.2022.87766.1434.
- Chen C, Hui Y, Chen Y, Qian C, Sun M. Loss of c-Cbl expression correlates with de-differentiation status and lymphatic metastasis in gastric cancer. Indian J Pathol Microbiol. 2019;62(4):549-55. doi: 10.4103/IJPM.IJPM_824_18.
- Chen J, Li S, Zhou S, Cao S, Lou Y, Shen H, et al. Kinesin superfamily protein expression and its association with progression and prognosis in hepatocellular carcinoma. J Cancer Res Ther. 2017;13(4):651-9. doi: 10.4103/jcrt.JCRT_491_17.
- Fischer M, Grundke I, Sohr S, Quaas M, Hoffmann S, Knörck A, et al. p53 and cell cycle dependent transcription of kinesin family member 23 (KIF23) is controlled via a CHR promoter element bound by DREAM and MMB complexes. PLoS One. 2013;8(5):e63187. doi: 10.1371/journal.pone.0063187.
- Iltzsche F, Simon K, Stopp S, Pattschull G, Francke S, Wolter P, et al. An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma. 2017;36(1):110-21. doi: 10.1038/onc.2016.181.
- Takahashi S, Fusaki N, Ohta S, Iwahori Y, Iizuka Y, Inagawa K, et al. Downregulation of KIF23 suppresses glioma proliferation. J Neurooncol. 2012;106(3):519-29. doi: 10.1007/s11060-011-0706-2.
- Vikberg AL, Vooder T, Lokk K, Annilo T, Golovleva I. Mutation analysis and copy number alterations of KIF23 in non-small-cell lung cancer exhibiting KIF23 over-expression. Onco Targets Ther. 2017;10:4969-79. doi: 10.2147/OTT.S138420.
- Liyasova MS, Ma K, Lipkowitz S. Molecular pathways: cbl proteins in tumorigenesis and antitumor immunity-opportunities for cancer treatment. Clin Cancer Res. 2015;21(8):1789-94. doi: 10.1158/1078-0432.CCR-13-2490.
- Shashar M, Siwak J, Tapan U, Lee SY, Meyer RD, Parrack P, et al. c-Cbl mediates the degradation of tumorigenic nuclear β-catenin contributing to the heterogeneity in Wnt activity in colorectal tumors. 2016;7(44):71136-50. doi: 10.18632/oncotarget.12107.
- Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Miwa S, et al. Pathobiological characteristics of intestinal and diffuse-type gastric carcinoma in Japan: an immunostaining study on the tissue microarray. J Clin Pathol. 2007;60(3):273-7. doi: 10.1136/jcp.2006.038778.
- In H, Solsky I, Palis B, Langdon-Embry M, Ajani J, Sano T. Validation of the 8th Edition of the AJCC TNM Staging System for Gastric Cancer using the National Cancer Database. Ann Surg Oncol. 2017;24(12):3683-91. doi: 10.1245/s10434-017-6078-x.
- Ní Leidhin C, Redmond CE, Cahalane AM, Heneghan HM, Motyer R, Ryan ER, et al. Radical resection of a late-relapsed testicular germ cell tumour: hepatectomy, cavotomy, and thrombectomy. Case Rep Surg. 2014;2014:713049. doi: 10.1155/2014/713049.
- Manning L, O'Rourke KI, Knowles DP, Marsh SA, Spencer YI, Moffat E, et al. A collaborative Canadian-United Kingdom evaluation of an immunohistochemistry protocol to diagnose bovine spongiform encephalopathy. J Vet Diagn Invest. 2008;20(4):504-8. doi: 10.1177/104063870802000416.
- Li XL, Ji YM, Song R, Li XN, Guo LS. KIF23 promotes gastric cancer by stimulating cell proliferation. Dis Markers. 2019;2019:9751923. doi: 10.1155/2019/9751923.
- Xiao SM, Xu R, Tang XL, Ding Z, Li JM, Zhou X. Conversion therapy for advanced gastric cancer with trastuzumab combined with chemotherapy: A case report. Oncol Lett. 2018;16(2):2085-90. doi: 10.3892/ol.2018.8942.
- Liu Y, Chen H, Dong P, Xie G, Zhou Y, Ma Y, Yet al. KIF23 activated Wnt/β-catenin signaling pathway through direct interaction with Amer1 in gastric cancer. Aging (Albany NY). 2020;12(9):8372-96. doi: 10.18632/aging.103146.
- Liljeholm M, Irvine AF, Vikberg AL, Norberg A, Month S, Sandström H, et al. Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF23. Blood. 2013;6;121(23):4791-9. doi: 10.1182/blood-2012-10-461392.
- Isakson P, Lystad AH, Breen K, Koster G, Stenmark H, Simonsen A. TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy. Autophagy. 2013;9(12):1955-64. doi: 10.4161/auto.26085.
- Sun L, Zhang C, Yang Z, Wu Y, Wang H, Bao Z, et al. KIF23 is an independent prognostic biomarker in glioma, transcriptionally regulated by TCF-4. Oncotarget. 2016;7(17):24646-55. doi: 10.18632/oncotarget.8261.
- Ye L, Li H, Zhang F, Lv T, Liu H, Song Y. Expression of KIF23 and Its Prognostic Role in Non-small Cell Lung Cancer: Analysis Based on the Data-mining of Oncomine. [Article in Chinese] Zhongguo Fei Ai Za Zhi. 2017;20;20(12):822-6.doi: 10.3779/j.issn.1009-3419.2017.12.05.
- Murakami H, Ito S, Tanaka H, Kondo E, Kodera Y, Nakanishi H. Establishment of new intraperitoneal paclitaxel-resistant gastric cancer cell lines and comprehensive gene expression analysis. Anticancer Res. 2013;33(10):4299-307.
- Wang Y, Chen L, Wu Z, Wang M, Jin F, Wang N, et al. miR-124-3p functions as a tumor suppressor in breast cancer by targeting CBL. BMC Cancer. 2016;16(1):826. doi: 10.1186/s12885-016-2862-4.
- Yao S, Zheng P, Wu H, Song LM, Ying XF, Xing C, et al. Erbin interacts with c-Cbl and promotes tumourigenesis and tumour growth in colorectal cancer by preventing c-Cbl-mediated ubiquitination and down-regulation of EGFR. J Pathol. 2015;236(1):65-77. doi: 10.1002/path.4502.
- Wei TT, Lin YC, Lin PH, Shih JY, Chou CW, Huang WJ, et al. Induction of c-Cbl contributes to anti-cancer effects of HDAC inhibitor in lung cancer. 2015;6(14):12481-92. doi: 10.18632/oncotarget.3489.
- Seong MW, Park JH, Yoo HM, Yang SW, Oh KH, Ka SH, et al. c-Cbl regulates αPix-mediated cell migration and invasion. Biochem Biophys Res Commun. 2014;455(3-4):153-8. doi: 10.1016/j.bbrc.2014.10.129.
- Nihal M, Wood GS. c-CBL regulates melanoma proliferation, migration, invasion and the FAK-SRC-GRB2 nexus. Oncotarget. 2016;7(33):53869-80. doi: 10.18632/oncotarget.10861.
- Ma L, Zhu W, Wang Q, Yang F, Qian J, Xu T, et al. JWA down-regulates HER2 expression via c-Cbl and induces lapatinib resistance in human gastric cancer cells. 2016;7(44):71790-801. doi: 10.18632/oncotarget.12374.
)