title: Upregulated HOXC8 Expression Is Associated with Poor Prognosis and Oxaliplatin Resistance in Hepatocellular Carcinoma.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. It is indispensable to understanding molecular mechanisms of HCC progression and to developing clinically useful biomarkers for this disease.
  
  
  OBJECTIVE
  In this article, we examined whether HOXC8 was associated with the poor prognosis of hepatocellular carcinoma and explored the possible underlying mechanism.
  
  
  METHODS
  The HOXC8 and Ki67 expression levels in 86 patients with hepatocellular carcinoma were examined using immunohistochemistry. HOXC8 levels in HCC cells were downregulated by siRNA transfection. The cycle progression and cell proliferation status of HCC cells and the oxaliplatin effectiveness were evaluated by flow cytometry and CCK-8 assay. HOXC8, CyclinD1, PCNA, Nkd2, and cleaved caspase-3 levels were detected by western blot.
  
  
  RESULTS
  HOXC8 was upregulated in HCC tissues, compared with adjacent non-tumor ones. HOXC8 expression levels in 86 patients with hepatocellular carcinoma were positively correlated with histological grade. Univariate and multivariate survival analysis revealed that HOXC8 was a significant predictor for overall survival of HCC patients. HOXC8 siRNA knockdown delayed the G1-S phase transition, inhibited cell proliferation, and attenuated resistance to oxaliplatin.
  
  
  CONCLUSIONS
  HOXC8 promoted HCC proliferation and predicted poor prognosis. Furthermore, upregulated HOXC8 expression was associated with oxaliplatin resistance in hepatocellular carcinoma.
authors.affiliation: Department of Radiotherapy, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Pan
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, the Second Peoples Hospital of Nan Tong, 43 Tangzha Xinglong Road, Nantong, 226002, Jiangsu Province, People's Republic of China.
authors.forename: Xiubing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Wenkai
authors.initials: W
authors.lastname: Ni
authors.affiliation: Department of Medical Oncology, the Second Peoples Hospital of Nan Tong, 43 Tangzha Xinglong Road, Nantong, 226002, Jiangsu Province, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Medical Oncology, the Second Peoples Hospital of Nan Tong, 43 Tangzha Xinglong Road, Nantong, 226002, Jiangsu Province, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, the Second Peoples Hospital of Nan Tong, 43 Tangzha Xinglong Road, Nantong, 226002, Jiangsu Province, People's Republic of China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathogen Biology, Jiangsu Province Key Laboratory for Information and Molecular Drug Target, Nantong University, 9 Qiangyuan Road, Nantong, 226019, Jiangsu Province, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pathogen Biology, Jiangsu Province Key Laboratory for Information and Molecular Drug Target, Nantong University, 9 Qiangyuan Road, Nantong, 226019, Jiangsu Province, People's Republic of China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Pathogen Biology, Jiangsu Province Key Laboratory for Information and Molecular Drug Target, Nantong University, 9 Qiangyuan Road, Nantong, 226019, Jiangsu Province, People's Republic of China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors.forename: Runzhou
authors.initials: R
authors.lastname: Ni
authors.affiliation: Department of Radiotherapy, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province, People's Republic of China. chenby1954chen@163.com.
authors.forename: Buyou
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, the Second Peoples Hospital of Nan Tong, 43 Tangzha Xinglong Road, Nantong, 226002, Jiangsu Province, People's Republic of China. shiweidong2015@163.com.
authors.forename: Weidong
authors.initials: W
authors.lastname: Shi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002135:Calcium-Binding Proteins; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016016:Proportional Hazards Models; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C489815:HOXC8 protein, human; D018398:Homeodomain Proteins; D019394:Ki-67 Antigen; C449092:NKD2 protein, human; D009944:Organoplatinum Compounds; D018809:Proliferating Cell Nuclear Antigen; D000077150:Oxaliplatin; D019938:Cyclin D1; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: HOXC8; Hepatocellular carcinoma; Oxaliplatin resistance; Poor prognosis