title: Digital transcript profile analysis with aRNA-LongSAGE validates FERMT1 as a potential novel prognostic marker for colon cancer.
abstract: OBJECTIVE
  To use gene transcript profiling to identify cancer-associated gene expression.
  
  
  METHODS
  Methods included (i) marker discovery using laser capture microdissection (LCM)-assisted specimen preparation and antisense RNA-long serial analysis of gene expression (aRNA-LongSAGE) on matched colon cancer and uninvolved colon tissue specimens (n = 5). Candidate tumor-associated genes were selected by combining the LongSAGE libraries reported herein with our previous colon cancer LCM-microarray transcript profiling data; (ii) marker selection and validation by quantitative real-time PCR (n = 15) and immunohistochemistry (n = 31); and (iii) independent validation on multiple tissue microarray (n = 203).
  
  
  RESULTS
  Among 30 upregulated and 73 downregulated genes, upregulation of fermitin family member 1 (FERMT1), adenosylhomocysteinase (AHCY), secernin 1 (SCRN1), and SAC3 domain-containing protein 1 (SAC3D1) expression and downregulation of IgJ and MALL expression in colon cancer were confirmed by quantitative PCR. FERMT1 and AHCY protein expression was also upregulated in colon cancer compared with uninvolved colon mucosa, and FERMT1 expression showed upregulation in colon adenoma. Patients with moderate/strong tumor FERMT1 protein expression (n = 122) showed significantly poorer overall survival (OS; P = 0.011) and disease-free survival (DFS; P = 0.005) than patients with negative/weak tumor FERMT1 protein expression (n = 81). Multivariate Cox regression analysis showed that FERMT1 protein expression was also an independent prognostic factor for OS (P = 0.018) and DFS (P = 0.009). In addition, upregulated FERMT1 protein expression appeared to have some specificity among alimentary tract tumors.
  
  
  CONCLUSIONS
  FERMT1 is a novel prognostic factor for colon carcinoma.
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Fan
authors.forename: Dongwang
authors.initials: D
authors.lastname: Yan
authors.forename: Mujian
authors.initials: M
authors.lastname: Teng
authors.forename: Huamei
authors.initials: H
authors.lastname: Tang
authors.forename: Chongzhi
authors.initials: C
authors.lastname: Zhou
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Wang
authors.forename: Dawei
authors.initials: D
authors.lastname: Li
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Qiu
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D015698:Genomic Library; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D012815:Signal Processing, Computer-Assisted; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C475301:FERMT1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger