Introduction A cancerized field is an area of abnormal tissue in the vicinity of a cancer that macroscopically appears normal, and which may be responsible for neoplastic recurrence. Evidence from keratin-8-deficient mice suggests that it is important for colonic mucosa stability. Keratin 8 (K8) levels are also up-regulated in the immediate area around colorectal carcinomas. Moreover, the anti-colorectal cancer action of butyrate may, at least in part, be mediated by K8. Therefore we investigated levels of K8, and its association with butyrate levels, in human sporadic colorectal adenomas.
Methods Patients (n = 8) with an adenoma detected on routine colonoscopy had biopsies taken from three sites (adenoma [AD], bowel wall opposite adenoma [CO] and mid-sigmoid colon [MS]). Mid-sigmoid biopsies were also taken from patients (n = 8) with no colonic pathology (N). Intermediate filaments from the biopsies were extracted and solubilised, prior to pooling according to site and exposure to high (H) or low (L) butyrate within the colonic lumen (determined via faecal sampling). K8 levels were then determined using iTRAQ. GeneBio Phenyx software and the UniProt protein knowledgebase were used for protein identification. iTRAQ results were validated using Western immunoblot analysis.
Results Independent of the butyrate level, K8 was increased in pathological tissue (AD, CO and MS) when compared to non-pathological tissue (figure 1). A high butyrate environment was associated with increased K8 levels compared to low butyrate samples (figure 1). Adenoma samples from both butyrate groups demonstrated a lower molecular weight form of K8 (figure 2; red arrows).
Conclusion Increased K8 may represent a response to malignant transformation to stabilise colonic mucosa. Human colonic adenomas exhibit a lower molecular weight form of K8 not seen in normal colorectal mucosa, possibly associated with the degradome. The anti-neoplastic action of butyrate may be mediated via up-regulation or altered solubility of K8.
Disclosure of Interest None Declared.
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