title: Alternative mRNA splicing of liver intestine-cadherin in hepatocellular carcinoma.
abstract: OBJECTIVE
  To identify alternative splicing of the liver intestine-cadherin (LI-cadherin) gene in hepatocellular carcinoma (HCC) and correlate its aberrant expression with clinical outcomes.
  
  
  METHODS
  Reverse transcription-PCR (RT-PCR) and quantitative real-time RT-PCR were used to examine alternative mRNA splicing and mRNA level of LI-cadherin in 50 paired tumor-peritumor tissues of 50 HCC and 8 normal liver specimens. The minigene exon-trapping strategy was employed to investigate the splicing mechanism introduced by nucleotide polymorphisms. Association of LI-cadherin splicing with tumor venous infiltration, first-year tumor recurrence, and overall survival after partial hepatectomy were determined.
  
  
  RESULTS
  Alternative mRNA splicing of LI-cadherin was identified in half of the HCC specimens. Sequencing analysis indicated the loss of exon 7 in the spliced LI-cadherin gene. LI-cadherin mRNA was up-regulated from 2.58-fold to 800-fold in over 80% of HCC samples when compared with normal liver by quantitative PCR. Furthermore, nucleotide polymorphisms were identified in putative branch point at IVS6 + 35 (intron 6) as well as in coding sequence 651 (exon 6) in HCC tissues, which may affect alternative mRNA splicing. Clinically, those patients who harbored the alternative splicing of LI-cadherin were strongly associated with shorter overall survival time (P < 0.01) as well as higher incidences of tumor recurrences and venous infiltration (both P < 0.05) after hepatectomy.
  
  
  CONCLUSIONS
  Over-expression of LI-cadherin was frequently detected in liver cancer patients. Aberrant alternative splicing of LI-cadherin was detected in 50% of HCC specimens and its clinical significance hinted at early tumor recurrence and poor overall survival of HCC patients.
authors.affiliation: Department of Surgery, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong.
authors.forename: Xiao Qi
authors.initials: XQ
authors.lastname: Wang
authors.forename: John M
authors.initials: JM
authors.lastname: Luk
authors.forename: Pauline P
authors.initials: PP
authors.lastname: Leung
authors.forename: Bonnie W
authors.initials: BW
authors.lastname: Wong
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Stanbridge
authors.forename: Sheung Tat
authors.initials: ST
authors.lastname: Fan
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D002522:Chlorocebus aethiops; D005091:Exons / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014162:Transfection
chemical_list: C490584:CDH17 protein, human; D015820:Cadherins; D012333:RNA, Messenger; D012334:RNA, Neoplasm