SEL1L, an UPR response protein, a potential marker of colonic cell transformation

Hassan Ashktorab, William Green, Giovanna Finzi, Fausto Sessa, Mehdi Nouraie, Edward L. Lee, Annalisa Morgano, Antonio Moschetta, Monica Cattaneo, Renato Mariani-Costantini, Hassan Brim, Ida Biunno

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17 Scopus citations

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. Aim 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 mucosaundergoing 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.

Original languageEnglish (US)
Pages (from-to)905-912
Number of pages8
JournalDigestive Diseases and Sciences
Volume57
Issue number4
DOIs
StatePublished - Apr 1 2012

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Keywords

  • Colorectal cancers
  • Paneth's cells
  • SEL1L expression

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

Cite this

Ashktorab, H., Green, W., Finzi, G., Sessa, F., Nouraie, M., Lee, E. L., Morgano, A., Moschetta, A., Cattaneo, M., Mariani-Costantini, R., Brim, H., & Biunno, I. (2012). SEL1L, an UPR response protein, a potential marker of colonic cell transformation. Digestive Diseases and Sciences, 57(4), 905-912. https://doi.org/10.1007/s10620-011-2026-y