title: B3GNT3 Expression Is a Novel Marker Correlated with Pelvic Lymph Node Metastasis and Poor Clinical Outcome in Early-Stage Cervical Cancer.
abstract: BACKGROUND
  The β1,3-N-acetylglucosaminyltransferase-3 gene (B3GNT3) encodes a member of the B3GNT family that functions as the backbone structure of dimeric sialyl-Lewis A and is involved in L-selectin ligand biosynthesis, lymphocyte homing and lymphocyte trafficking. B3GNT3 has been implicated as an important element in the development of certain cancers. However, the characteristics of B3GNT3 in the development and progression of cancer remain largely unknown. Thus, our study aimed to investigate the expression pattern and the prognostic value of B3GNT3 in patients with early-stage cervical cancer.
  
  
  METHODS
  The mRNA and protein levels of B3GNT3 expression were examined in eight cervical cancer cell lines and ten paired cervical cancer tumors, using real-time PCR and western blotting, respectively. Immunohistochemistry (IHC) was used to analyze B3GNT3 protein expression in paraffin-embedded tissues from 196 early-stage cervical cancer patients. Statistical analyses were applied to evaluate the association between B3GNT3 expression scores and clinical parameters, as well as patient survival.
  
  
  RESULTS
  B3GNT3 expression was significantly upregulated in cervical cancer cell lines and lesions compared with normal cells and adjacent noncancerous cervical tissues. In the 196 cases of tested early-stage cervical cancer samples, the B3GNT3 protein level was positively correlated with high risk TYPES of human papillomavirus (HPV) infection (P = 0.026), FIGO stage (P < 0.001), tumor size (P = 0.025), tumor recurrence (P = 0.004), vital status (P < 0.001), concurrent chemotherapy and radiotherapy (P = 0.016), lymphovascular space involvement (P = 0.003) and most importantly, lymph node metastasis (P = 0.003). Patients with high B3GNT3 expression had a shorter overall survival (OS) and disease-free survival (DFS) compared with those with low expression of this protein. Multivariate analysis suggested that B3GNT3 expression is an independent prognostic indicator for cervical cancer patients.
  
  
  CONCLUSIONS
  Our study demonstrated that elevated B3GNT3 expression is associated with pelvic lymph node metastasis and poor outcome in early-stage cervical cancer patients. B3GNT3 may be a novel prognostic marker and therapeutic target for the treatment of cervical cancer.
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Weijing
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Urology, Wuhan Union Hospital of Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Teng
authors.initials: T
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Chunhao
authors.initials: C
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Libing
authors.initials: L
authors.lastname: Song
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D019041:L-Selectin / Q000096:biosynthesis; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics*; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D019041:L-Selectin; C000609418:B3GNT3 protein, human; D017351:N-Acetylglucosaminyltransferases