title: SEL1L, an UPR response protein, a potential marker of colonic cell transformation.
abstract: BACKGROUND
  SEL1L gene product is implicated in the endoplasmic reticulum (ER)-associated protein degradation and Unfolded Protein Response pathways. This gene and associated miRNAs have been indicated as predictive and prognostic markers of pancreatic cancer.
  
  
  OBJECTIVE
  Explore the role of SEL1L in colorectal cancer (CRC) progression.
  
  
  METHODS
  SEL1L expression was analysed immunohistochemically in 153 adenomas and 71 CRCs from African American and North Italian patients. The distribution of stained cells was determined by computing median and inter quartile range. The receiver operating characteristics plot was used as discriminate power of SEL1L expression, CRC diagnosis and the effects on patient survival.
  
  
  RESULTS
  SEL1L was low in normal mucosa and confined to few scattered cells at the base crypt of the villi and in the foveolar glandular compartment. The highest levels were in Paneth cells within the lysosomes. The enterocytic progenitor cells and mature enterocytes showed less cytoplasmic staining. In CRCs, SEL1L expression significantly correlated with the progression from adenoma to carcinoma (P = 0.0001) being stronger in well-to-moderately differentiated cancers. No correlation was found with other clinicopathological characteristics or ethnicity.
  
  
  CONCLUSIONS
  SEL1L expression is a potential CRC tissue biomarker since its expression is significantly higher in adenoma cells with respect to normal mucosa. The levels of expression decrease sensibly in undifferentiated CRC cancers. Interestingly, Paneth cells contain high levels of SEL1L protein that could indicate pre-neoplastic mucosa undergoing neoplastic transformation. Since SEL1L's major function lies within ER stress and active ERAD response, it may identify CRCs with differentiated secretory phenotype and acute cellular stress.
authors.affiliation: Department of Medicine and Cancer Center, Howard University College of Medicine, 2041 Georgia Avenue, NW, Washington, DC 20060, USA. hashktorab@howard.edu
authors.forename: Hassan
authors.initials: H
authors.lastname: Ashktorab
authors.forename: William
authors.initials: W
authors.lastname: Green
authors.forename: Giovanna
authors.initials: G
authors.lastname: Finzi
authors.forename: Fausto
authors.initials: F
authors.lastname: Sessa
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nouraie
authors.forename: Edward L
authors.initials: EL
authors.lastname: Lee
authors.forename: Annalisa
authors.initials: A
authors.lastname: Morgano
authors.forename: Antonio
authors.initials: A
authors.lastname: Moschetta
authors.forename: Monica
authors.initials: M
authors.lastname: Cattaneo
authors.forename: Renato
authors.initials: R
authors.lastname: Mariani-Costantini
authors.forename: Hassan
authors.initials: H
authors.lastname: Brim
authors.forename: Ida
authors.initials: I
authors.lastname: Biunno
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019879:Paneth Cells / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis; D056811:Unfolded Protein Response
chemical_list: D014408:Biomarkers, Tumor; D011506:Proteins; C117384:SEL1L protein, human