title: Aldolase B inhibits metastasis through Ten-Eleven Translocation 1 and serves as a prognostic biomarker in hepatocellular carcinoma.
abstract: BACKGROUND
  Downregulation of Aldolase B (ALDOB) has been reported in hepatocellular carcinoma. However, its clinical significance and its role in pathogenesis of HCC remain largely unknown.
  
  
  METHODS
  We analyzed the expression of ALDOB and its clinical features in a large cohort of 313 HCC patients using tissue microarray and immunohistochemistry. Moreover, the function of stably overexpressed ALDOB in HCC cells was explored in vitro and in vivo. Gene expression microarray analysis was performed on ALDOB-overexpressing SMMC7721 cells to elucidate its mechanism of action.
  
  
  RESULTS
  ALDOB downregulation in HCC was significantly correlated with aggressive characteristics including absence of encapsulation, increased tumor size (>5 cm) and early recurrence. ALDOB downregulation was indicative of a shorter recurrence-free survival (RFS) and overall survival (OS) for all HCC patients and early-stage HCC patients (BCLC 0-A and TNM I stage patients). Multiple analyses revealed that ALDOB downregulation was an independent risk factor of RFS and OS. Stable expression of ALDOB in HCC cell lines reduced cell migration in vitro and inhibited lung metastasis, intrahepatic metastasis, and reduced circulating tumor cells in vivo. Mechanistically, we found that cells stably expressing ALDOB show elevated Ten-Eleven Translocation 1 (TET1) expression. Moreover, ALDOB expressing cells have higher levels of methylglyoxal than do control cells, which can upregulate TET1 expression.
  
  
  CONCLUSIONS
  The downregulation of ALDOB could indicate a poor prognosis for HCC patients, and therefore, ALDOB might be considered a prognostic biomarker for HCC, especially at the early stage. In addition, ALDOB inhibits the invasive features of cell lines partly through TET1 expression.
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, 200438, Shanghai, P.R. China. tqftxl@163.com.
authors.forename: Qi-Fei
authors.initials: QF
authors.lastname: Tao
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, 200438, Shanghai, P.R. China. yuanshengx@126.com.
authors.forename: Sheng-Xian
authors.initials: SX
authors.lastname: Yuan
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China. yangfusq1997@hotmail.com.
authors.forename: Fu
authors.initials: F
authors.lastname: Yang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, 200438, Shanghai, P.R. China. 409106966@qq.com.
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, 200438, Shanghai, P.R. China. yangyuan.ehbh@gmail.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China. yuan3239@163.com.
authors.forename: Ji-Hang
authors.initials: JH
authors.lastname: Yuan
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, 200438, Shanghai, P.R. China. wangzhenguang82@163.com.
authors.forename: Zhen-Guang
authors.initials: ZG
authors.lastname: Wang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, 200438, Shanghai, P.R. China. xuqingguo8866@126.com.
authors.forename: Qing-Guo
authors.initials: QG
authors.lastname: Xu
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, 200438, Shanghai, P.R. China. 273825776@qq.com.
authors.forename: Kong-Ying
authors.initials: KY
authors.lastname: Lin
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, 200438, Shanghai, P.R. China. cjxm56@126.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, 200438, Shanghai, P.R. China. 1274432278@qq.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, 200438, Shanghai, P.R. China. 778053608@qq.com.
authors.forename: Wei-Long
authors.initials: WL
authors.lastname: Huang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, 200438, Shanghai, P.R. China. 552350432@qq.com.
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Teng
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China. shenyueji3@163.com.
authors.forename: Chuan-Chuan
authors.initials: CC
authors.lastname: Zhou
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China. wfsjz70@gmail.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: The Department of Medical Genetics, Second Military Medical University, Shanghai, China. shsun@vip.sina.com.
authors.forename: Shu-Han
authors.initials: SH
authors.lastname: Sun
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, 200438, Shanghai, P.R. China. ehphwp3@126.com.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhou
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D006899:Mixed Function Oxygenases; D009362:Neoplasm Metastasis; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; D005634:Fructose-Bisphosphate Aldolase