title: Activation of the sonic hedgehog pathway and its prognostic impact in patients with gastric cancer.
abstract: BACKGROUND
  The sonic hedgehog (SHH) signaling pathway is critical in fetal organogenesis. Activation of the SHH pathway has been associated with several types of human cancer; however, the clinical impact of SHH activation in patients with gastric cancer is still unknown.
  
  
  METHODS
  The present study included 41 patients with gastric cancer who underwent gastrectomy between 2000 and 2004. SHH, Patched-1 (PTCH1), Smoothened (SMO) and Glioma-associated oncogene-1 (GLI1) were examined immunohistochemically, and these of mRNAs from the cancer lesions were evaluated using real-time quantitative RT-PCR.
  
  
  RESULTS
  Immunohistological expressions of SHH-related molecules were relatively intense in cancer tissue, but no significant correlation was found with any clinicopathological factors of tumor. PTCH1 was only the molecule associated with poor prognosis of patients with differentiated type of tumor. For mRNA analysis, a significant correlation was demonstrated between certain clinicopathological factors and PTCH1, SMO or/and GLI1 mRNA levels. High levels of SHH and PTCH1 mRNA were associated with poor prognosis. Multivariate analysis demonstrated the PTCH1 mRNA level and liver metastasis as significant independent prognostic factors.
  
  
  CONCLUSIONS
  PTCH1 expression in the SHH pathway was possibly involved in gastric cancer tumor progression, and could be a useful indicator for the prognosis of gastric cancer.
authors.affiliation: First Department of Surgery, Fukushima Medical University, Fukushima, Japan.
authors.forename: Zenichiro
authors.initials: Z
authors.lastname: Saze
authors.forename: Masanori
authors.initials: M
authors.lastname: Terashima
authors.forename: Michihiko
authors.initials: M
authors.lastname: Kogure
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Ohsuka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Mitsukazu
authors.initials: M
authors.lastname: Gotoh
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001707:Biopsy, Needle; D015331:Cohort Studies; D018076:DNA, Complementary / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005743:Gastrectomy / Q000379:methods; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D011956:Receptors, Cell Surface / Q000235:genetics*; D012189:Retrospective Studies; D018570:Risk Assessment; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D053823:Hedgehog Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface