title: Evaluation of KIF23 variant 1 expression and relevance as a novel prognostic factor in patients with hepatocellular carcinoma.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China. sunxt0129@163.com.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Center of Hepatobiliary Surgery, People's Hospital, Peking University Health Science Center, Beijing, China. zybi1998@163.com.
authors.forename: Zhongtian
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China. songxiao@bjmu.edu.cn.
authors.forename: Xiao
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China. wangjingjing@bjmu.edu.cn.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China. liyan@bjmu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China. qianxiaoping@bjmu.edu.cn.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Qian
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China. zhangyu@bjmu.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China. yinyanhui@bjmu.edu.cn.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C092935:KIF23 protein, human; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms