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Downregulation of cornulin in esophageal squamous cell carcinoma

Harsh Pawar1, Jagadeesha Maharudraiah, Manoj Kumar Kashyap

  • 1Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.

Acta Histochemica
|May 8, 2012
PubMed

Insights

Cornulin (CRNN) protein is significantly downregulated in esophageal squamous cell carcinoma (ESCC) tissues. This loss of cornulin expression occurs early in esophageal cancer development, suggesting its role in normal esophageal health.

Area of Science:

  • Oncology
  • Molecular Biology
  • Proteomics

Background:

  • Early molecular events in esophageal squamous cell carcinoma (ESCC) development remain largely unknown.
  • Key molecules driving ESCC pathogenesis require identification.
  • Previous proteomic studies identified cornulin as downregulated in ESCC.

Purpose of the Study:

  • To validate the downregulation of cornulin (CRNN) in a large cohort of ESCC patients.
  • To investigate the expression pattern of cornulin in normal esophageal epithelium and ESCC tissues.
  • To assess the potential role of cornulin loss in esophageal carcinogenesis.

Main Methods:

  • Quantitative proteomics using isobaric tags for relative and absolute quantitation (iTRAQ).
  • Immunohistochemical validation of cornulin expression on tissue microarrays (TMAs) from 266 ESCC patients.
  • Analysis of cornulin localization in normal esophageal mucosa and ESCC tissues.

Main Results:

  • Cornulin was confirmed to be significantly downregulated in 89% of ESCC tissues compared to normal epithelium.
  • Cornulin expression was detected in the prickle and functional cell layers of normal esophageal mucosa, primarily in the cytoplasm and perinuclear region.
  • Most ESCC tissues exhibited minimal to no cornulin expression in carcinoma or stromal cells.

Conclusions:

  • Cornulin is a key molecule in normal esophageal epithelium.
  • Loss of cornulin expression is a frequent event during the transition from normal to neoplastic esophageal epithelium.
  • Cornulin downregulation may serve as an early indicator or contributor to ESCC development.

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