PTU-056 Loss of cathelicidin (LL-37) is associated with colorectal cancer progression. (8th June 2018)

• Record Type: Journal Article
• Authors: Porter, Ross J; Murray, Graeme I; Wang, Ji M; Yoshimura, Teizo; McLean, Mairi H
• Is Part Of: Gut. Volume 67(2018)Supplement 1
• Page Start: A199
• Page End: A199
• Publication Date: 2018-06-08
• Subjects: Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2018-BSGAbstracts.397
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Introduction: Cathelicidin (LL-37) is an innate anti-microbial peptide. Previous in vitro studies suggest a protective role in colonic carcinogenesis. Our recent pre-clinical data revealed that genetic knock out of cathelicidin led to increased size and number of colorectal tumours in the azoxymethane mediated murine model of colorectal cancer (CRC). Cathelicidin expression has not been characterised in human colorectal cancer. Methods: Intensity of epithelial cytoplasmic LL-37 was assessed immunohistochemically in a tissue microarray representing 650 colorectal cancers and 50 paired normal colorectal mucosa samples. Tissue was obtained from chemotherapy and radiotherapy naïve patients obtained at time of surgery for primary colonic cancer, sourced from the Grampian Tissue Biorepository. Ethical approval was granted by the Grampian Biorepository Scientific Access Group. Clinico-pathological data were available for each case, including survival up to 18.2 years post-resection. Expression intensity of LL-37 was independently assessed by two observers, blind to clinico-pathological data, as absent, weak, moderate or strong. Descriptive analysis, χ 2 test, Fisher's exact test and log-rank survival analysis was performed using IBM SPSS Statistics (Version 24.0.0.0). Results: The expression of cytoplasmic LL-37 was weaker in colorectal cancer compared to normal colonic epithelium (p<0.001). Increased intensity of LL-37 expression was present in patients staged Dukes A compared to Dukes B (p=0.004) or Dukes C (p=0.003). There was no correlation of LL-37 expression to tumour site, differentiation, extra-mural venous invasion or mismatch repair protein status. Normal colonic mucosa from patients with Dukes A CRC expressed stronger cytoplasmic LL-37 compared to normal colonic mucosa from patients with Dukes C CRC (p=0.031). There was no relationship between LL-37 expression and overall survival. Conclusions: Loss of epithelial cytoplasmic LL-37 is associated with progression of colorectal cancer, confirming translation of pre-clinical data to human disease. There may be a global field change in LL-37 expression in distant non-malignant cells as CRC progresses. The functional impact of this warrants further investigation and may reveal new insight into the pathogenesis of colorectal cancer.