title: A novel prognostic biomarker SPC24 up-regulated in hepatocellular carcinoma.
abstract: SPC24 is an important component of the nuclear division cycle 80 (Ndc80) kinetochore complex, which plays an essential role in the coupling of kinetochore to spindle microtubules (MTs) and the accurate segregation of chromosomes during mitosis. However, the functional role of SPC24 in hepatocellular carcinoma (HCC) remains unknown. Here, we detected the expression of SPC24 in HCC and analyzed its association with clinicopathologic features and prognosis of HCC patients. The expression of SPC24 mRNA was investigated in 212 cases of paired HCC and adjacent liver tissues by quantitative real-time PCR (qRT-PCR) and in the tissues of 20 HCC patients by semi-quantitative RT-PCR. Additionally, the expression of SPC24 protein was detected in 69 cases of HCC by immunohistochemistry (IHC) or in 2 cases of HCC tissues by Western-blotting. Furthermore, small interfering RNA (siRNA)-mediated silencing of SPC24 was employed in SMMC7721 and HepG2 human HCC cells to investigate cell proliferation, invasion and apoptosis. Survival curves were plotted using the Kaplan-Meier method, and differences in survival probability were obtained using the log-rank test. Independent predictors associated with disease-free survival (DFS) and overall survival (OS) were analyzed using the Cox proportional-hazards regression model. In this study, we showed that SPC24 was noticeably increased in HCC tissues compared to normal adjacent noncancerous tissues, at both mRNA and protein levels. High expression of SPC24 was significantly correlated with alpha-fetoprotein (AFP) (p = 0.044), median size (p = 0.030), tumor number (p = 0.019), and Barcelona-Clinic Liver Cancer (BCLC) stage (p = 0.015). Kaplan-Meier analysis showed that the DFS and OS of high SPC24 expression group was significantly shorter than that of low SPC24 expression group (p < 0.001; p = 0.001; respectively). The prognostic impact of SPC24 was further confirmed by stratified survival analysis. Importantly, multivariate analysis identified SPC24 upregualtion (p = 0.001), PVTT (p = 0.007), size of tumor > 5 cm (p < 0.001) as independent risk factors of DFS after resection, and SPC24 upregualtion (p < 0.001), PVTT (p = 0.029), size of tumor > 5 cm (p = 0.002), recurrence (p < 0.001) as independent prognostic factors for the OS of HCC patients. Additionally, siRNA-mediated silencing of SPC24 dramatically suppressed cell growth, adhesion, invasion and increased apoptosis in HCC cells. In conclusion, these results showed for the first time that SPC24 expression was significantly up-regulated in HCC, which may act as a novel prognostic biomarker for patients suffering from this deadly disease. Additionally, silence of SPC24 inhibiting HCC cell growth indicated that SPC24 may be a promising molecular target for HCC therapy.
authors.affiliation: Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People's Republic of China.
authors.forename: Pengpeng
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People's Republic of China.|Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, Guilin, Guangxi, People's Republic of China.
authors.forename: Junfei
authors.initials: J
authors.lastname: Jin
authors.affiliation: Disease Prevention and Control Center of Guilin, Guilin, Guangxi, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Xue-Zhong
authors.initials: XZ
authors.lastname: Yu
authors.affiliation: Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People's Republic of China.|Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, Guilin, Guangxi, People's Republic of China.
authors.forename: Weijia
authors.initials: W
authors.lastname: Liao
authors.affiliation: Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People's Republic of China.|Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, Guilin, Guangxi, People's Republic of China.
authors.forename: Songqing
authors.initials: S
authors.lastname: He
mesh_terms: D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D034622:RNA Interference; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D008869:Microtubule-Associated Proteins; C484695:SPC24 protein, human; D000509:alpha-Fetoproteins
keywords: SPC24; hepatocellular carcinoma; invasion; prognosis; proliferation