title: Slug is a predictor of poor prognosis in esophageal squamous cell carcinoma patients.
abstract: BACKGROUND
  Slug, a regulator of epithelial mesenchymal transition, was identified to be differentially expressed in esophageal squamous cell carcinoma (ESCC) using cDNA microarrays by our laboratory. This study aimed to determine the clinical significance of Slug overexpression in ESCC and determine its correlation with clinicopathological parameters and disease prognosis for ESCC patients.
  
  
  METHODS
  Immunohistochemical analysis of Slug expression was carried out in archived tissue sections from 91 ESCCs, 61 dysplastic and 47 histologically normal esophageal tissues. Slug immunopositivity in epithelial cells was correlated with clinicopathological parameters and disease prognosis over up to 7.5 years for ESCC patients.
  
  
  RESULTS
  Increased expression of Slug was observed in esophageal dysplasia [cytoplasmic, 24/61 (39.3%) cases, p = 0.001, odd's ratio (OR) = 4.7; nuclear, 11/61 (18%) cases, p < 0.001, OR = 1.36] in comparison with normal esophageal tissues. The Slug expression was further increased in ESCCs [cytoplasmic, 64/91 (70.3%) p < 0.001, OR = 10.0; nuclear, 27/91 (29.7%) p < 0.001, OR = 1.42]. Kaplan Meier survival analysis showed significant association of nuclear Slug accumulation with reduced disease free survival of ESCC patients (median disease free survival (DFS) = 6 months, as compared to those that did not show overexpression, DFS = 18 months; p = 0.006). In multivariate Cox regression analysis nuclear Slug expression [p= 0.005, Hazard's ratio (HR) = 2.269, 95% CI = 1.289 - 3.996] emerged as the most significant independent predictor of poor prognosis for ESCC patients.
  
  
  CONCLUSIONS
  Alterations in Slug expression occur in early stages of development of ESCC and are sustained during disease progression. Slug may serve as a diagnostic biomarker and as a predictor of poor disease prognosis to identify ESCC patients that are likely to show recurrence of the disease.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Md Raghibul
authors.initials: MR
authors.lastname: Hasan
authors.affiliation: School of Biotechnology, Guru Gobind Singh Indraprastha University, Delhi, India.
authors.forename: Rinu
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Anoop
authors.initials: A
authors.lastname: Saraya
authors.affiliation: Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
authors.forename: Tushar K
authors.initials: TK
authors.lastname: Chattopadhyay
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Siddartha
authors.initials: S
authors.lastname: DattaGupta
authors.affiliation: Department of Medicine, Endocrine Division, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada ; Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada ; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada ; Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology, Head and Neck Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada ; Department of Otolaryngology, Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Walfish
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Chauhan
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India ; Department of Medicine, Endocrine Division, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada ; Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada ; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada ; Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology, Head and Neck Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Ranju
authors.initials: R
authors.lastname: Ralhan
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D053208:Kaplan-Meier Estimate; D008297:Male; D011379:Prognosis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors