Skip to main content
Top
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Evaluation of KIF23 variant 1 expression and relevance as a novel prognostic factor in patients with hepatocellular carcinoma

Authors: Xiaotong Sun, Zhongtian Jin, Xiao Song, Jingjing Wang, Yan Li, Xiaoping Qian, Yu zhang, Yanhui Yin

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

KIF23 (kinesin family member 23) is a kinesin-like motor protein and plays an important role in cytokinesis. In search for genes associated with hepatocellular carcinoma (HCC) by cDNA microarray, we found that KIF23 was upregulated in HCC tissues. At present, much less is known about its expression and functions in tumor cells. In this work, we aimed to investigate the expression of KIF23 in HCC and the correlation between its expression and clinical features.

Methods

Total RNA was extracted from 16 HCC and paired adjacent non-cancerous tissues. The expressions of the two KIF23 splice variants (KIF23 V1 and KIF23 V2) in normal and HCC tissues were determined by reverse transcriptase polymerase chain reaction (RT-PCR). Polyclonal antibody specific to KIF23 V1 was prepared, and the specificity of the antibody was confirmed by siRNA knockdown and Western blotting experiments. KIF23 protein expression in HCC was examined by immunohistochemistry staining with anti-KIF23 V1 or anti-KIF23 (commercially available for recognizing both KIF23 V1 and V2) antibodies, respectively. Univariate and Multivariate Cox regression analyses were used to determine the correlation between KIF23 protein expression and overall survival of HCC patients.

Results

The two splicing variants of KIF23 mRNA were not detected in normal liver tissue by RT-PCR, but they were aberrantly expressed in HCC tissues. Immunohistochemistry staining with anti-KIF23 V1 antibody revealed that KIF23 V1 was mainly distributed in the nucleus, whereas the positive staining signals were predominantly in the cytoplasm when using anti-KIF23 antibody, suggesting that KIF23 V2 might localize in the cytoplasm of HCC cells. KIF23 V1 protein was detected in 57.6 % (83/144) HCC patients and the mean H-score was 42, while KIF23 V2 was detected in 94.4 % (135/143) HCC samples and the mean H-score was 68. Follow-up study showed that HCC patients with expression of KIF23 V1 had a longer 5-year survival (p = 0.0052), however, expression of KIF23 V2 protein did not associate with 3- and 5-year survival.

Conclusion

In this study we show for the first time that KIF23 V1 and V2 have different localizations in HCC cells. Furthermore, KIF23 V1 protein expression might be a marker of longer overall survival in HCC patients.
Literature
1.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.CrossRefPubMed Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.CrossRefPubMed
2.
go back to reference Xu L, Qian G, Tang L, Su J, Wang JS. Genetic variations of hepatitis B virus and serum aflatoxin-lysine adduct on high risk of hepatocellular carcinoma in Southern Guangxi, China. J Hepatol. 2010;53(4):671–6.CrossRefPubMed Xu L, Qian G, Tang L, Su J, Wang JS. Genetic variations of hepatitis B virus and serum aflatoxin-lysine adduct on high risk of hepatocellular carcinoma in Southern Guangxi, China. J Hepatol. 2010;53(4):671–6.CrossRefPubMed
3.
go back to reference Kew MC, Yu MC, Kedda MA, Coppin A, Sarkin A, Hodkinson J. The relative roles of hepatitis B and C viruses in the etiology of hepatocellular carcinoma in southern African blacks. Gastroenterology. 1997;112(1):184–7.CrossRefPubMed Kew MC, Yu MC, Kedda MA, Coppin A, Sarkin A, Hodkinson J. The relative roles of hepatitis B and C viruses in the etiology of hepatocellular carcinoma in southern African blacks. Gastroenterology. 1997;112(1):184–7.CrossRefPubMed
4.
go back to reference Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006;118(12):3030–44.CrossRefPubMed Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006;118(12):3030–44.CrossRefPubMed
5.
go back to reference Shi YY, Wang HC, Yin YH, Sun WS, Li Y, Zhang CQ, et al. Identification and analysis of tumour-associated antigens in hepatocellular carcinoma. Br J Cancer. 2005;92(5):929–34.CrossRefPubMedPubMedCentral Shi YY, Wang HC, Yin YH, Sun WS, Li Y, Zhang CQ, et al. Identification and analysis of tumour-associated antigens in hepatocellular carcinoma. Br J Cancer. 2005;92(5):929–34.CrossRefPubMedPubMedCentral
6.
go back to reference Yi Y, Wu H, Gao Q, He HW, Li YW, Cai XY, et al. Interferon regulatory factor (IRF)-1 and IRF-2 are associated with prognosis and tumor invasion in HCC. Ann Surg Oncol. 2013;20(1):267–76.CrossRefPubMed Yi Y, Wu H, Gao Q, He HW, Li YW, Cai XY, et al. Interferon regulatory factor (IRF)-1 and IRF-2 are associated with prognosis and tumor invasion in HCC. Ann Surg Oncol. 2013;20(1):267–76.CrossRefPubMed
7.
go back to reference Chen D, Xing W, Hong J, Wang M, Huang Y, Zhu C, et al. The beta2-adrenergic receptor is a potential prognostic biomarker for human hepatocellular carcinoma after curative resection. Ann Surg Oncol. 2012;19(11):3556–65.CrossRefPubMed Chen D, Xing W, Hong J, Wang M, Huang Y, Zhu C, et al. The beta2-adrenergic receptor is a potential prognostic biomarker for human hepatocellular carcinoma after curative resection. Ann Surg Oncol. 2012;19(11):3556–65.CrossRefPubMed
8.
go back to reference Nislow C, Lombillo VA, Kuriyama R, McIntosh JR. A plus-end-directed motor enzyme that moves antiparallel microtubules in vitro localizes to the interzone of mitotic spindles. Nature. 1992;359(6395):543–7.CrossRefPubMed Nislow C, Lombillo VA, Kuriyama R, McIntosh JR. A plus-end-directed motor enzyme that moves antiparallel microtubules in vitro localizes to the interzone of mitotic spindles. Nature. 1992;359(6395):543–7.CrossRefPubMed
9.
go back to reference Zhu C, Bossy-Wetzel E, Jiang W. Recruitment of MKLP1 to the spindle midzone/midbody by INCENP is essential for midbody formation and completion of cytokinesis in human cells. Biochem J. 2005;389(Pt 2):373–81.CrossRefPubMedPubMedCentral Zhu C, Bossy-Wetzel E, Jiang W. Recruitment of MKLP1 to the spindle midzone/midbody by INCENP is essential for midbody formation and completion of cytokinesis in human cells. Biochem J. 2005;389(Pt 2):373–81.CrossRefPubMedPubMedCentral
10.
go back to reference Chen MC, Zhou Y, Detrich 3rd HW. Zebrafish mitotic kinesin-like protein 1 (Mklp1) functions in embryonic cytokinesis. Physiol Genomics. 2002;8(1):51–66.CrossRefPubMed Chen MC, Zhou Y, Detrich 3rd HW. Zebrafish mitotic kinesin-like protein 1 (Mklp1) functions in embryonic cytokinesis. Physiol Genomics. 2002;8(1):51–66.CrossRefPubMed
11.
go back to reference Zhu C, Zhao J, Bibikova M, Leverson JD, Bossy-Wetzel E, Fan JB, et al. Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference. Mol Biol Cell. 2005;16(7):3187–99.CrossRefPubMedPubMedCentral Zhu C, Zhao J, Bibikova M, Leverson JD, Bossy-Wetzel E, Fan JB, et al. Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference. Mol Biol Cell. 2005;16(7):3187–99.CrossRefPubMedPubMedCentral
12.
go back to reference Liu X, Zhou T, Kuriyama R, Erikson RL. Molecular interactions of Polo-like-kinase 1 with the mitotic kinesin-like protein CHO1/MKLP-1. J Cell Sci. 2004;117(Pt 15):3233–46.CrossRefPubMed Liu X, Zhou T, Kuriyama R, Erikson RL. Molecular interactions of Polo-like-kinase 1 with the mitotic kinesin-like protein CHO1/MKLP-1. J Cell Sci. 2004;117(Pt 15):3233–46.CrossRefPubMed
13.
14.
go back to reference Valk K, Vooder T, Kolde R, Reintam MA, Petzold C, Vilo J, et al. Gene expression profiles of non-small cell lung cancer: survival prediction and new biomarkers. Oncology. 2010;79(3–4):283–92.CrossRefPubMed Valk K, Vooder T, Kolde R, Reintam MA, Petzold C, Vilo J, et al. Gene expression profiles of non-small cell lung cancer: survival prediction and new biomarkers. Oncology. 2010;79(3–4):283–92.CrossRefPubMed
15.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
16.
go back to reference Kuriyama R, Gustus C, Terada Y, Uetake Y, Matuliene J. CHO1, a mammalian kinesin-like protein, interacts with F-actin and is involved in the terminal phase of cytokinesis. J Cell Biol. 2002;156(5):783–90.CrossRefPubMedPubMedCentral Kuriyama R, Gustus C, Terada Y, Uetake Y, Matuliene J. CHO1, a mammalian kinesin-like protein, interacts with F-actin and is involved in the terminal phase of cytokinesis. J Cell Biol. 2002;156(5):783–90.CrossRefPubMedPubMedCentral
17.
go back to reference Hao J, Shen R, Li Y, Zhang Y, Yin Y. Cancer-testis antigen HCA587/MAGE-C2 interacts with BS69 and promotes its degradation in the ubiquitin-proteasome pathway. Biochem Biophys Res Commun. 2014;449(4):386–91.CrossRefPubMed Hao J, Shen R, Li Y, Zhang Y, Yin Y. Cancer-testis antigen HCA587/MAGE-C2 interacts with BS69 and promotes its degradation in the ubiquitin-proteasome pathway. Biochem Biophys Res Commun. 2014;449(4):386–91.CrossRefPubMed
18.
go back to reference Dong XY, Peng JR, Ye YJ, Chen HS, Zhang LJ, Pang XW, et al. Plac1 is a tumor-specific antigen capable of eliciting spontaneous antibody responses in human cancer patients. Int J Cancer. 2008;122(9):2038–43.CrossRefPubMed Dong XY, Peng JR, Ye YJ, Chen HS, Zhang LJ, Pang XW, et al. Plac1 is a tumor-specific antigen capable of eliciting spontaneous antibody responses in human cancer patients. Int J Cancer. 2008;122(9):2038–43.CrossRefPubMed
19.
go back to reference Christoph DC, Kasper S, Gauler TC, Loesch C, Engelhard M, Theegarten D, et al. betaV-tubulin expression is associated with outcome following taxane-based chemotherapy in non-small cell lung cancer. Br J Cancer. 2012;107(5):823–30.CrossRefPubMedPubMedCentral Christoph DC, Kasper S, Gauler TC, Loesch C, Engelhard M, Theegarten D, et al. betaV-tubulin expression is associated with outcome following taxane-based chemotherapy in non-small cell lung cancer. Br J Cancer. 2012;107(5):823–30.CrossRefPubMedPubMedCentral
20.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
21.
22.
go back to reference Fischer M, Grundke I, Sohr S, Quaas M, Hoffmann S, Knorck 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.CrossRefPubMedPubMedCentral Fischer M, Grundke I, Sohr S, Quaas M, Hoffmann S, Knorck 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.CrossRefPubMedPubMedCentral
Metadata
Title
Evaluation of KIF23 variant 1 expression and relevance as a novel prognostic factor in patients with hepatocellular carcinoma
Authors
Xiaotong Sun
Zhongtian Jin
Xiao Song
Jingjing Wang
Yan Li
Xiaoping Qian
Yu zhang
Yanhui Yin
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1987-1

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine