Using a combination of cytochrome P450 1B1 and β-catenin for early diagnosis and prevention of colorectal cancer

Background: Although fecal occult blood test and invasive endoscopic examination are common used to detect colorectal adenomas and cancers, non-invasive and specific biomarkers are still under investigation. The objective is to evaluate the biomarker CYP1B1 alone or in combination with aryl hydrocarbon receptor (AhR), nuclear β-catenin, p53 or bcl-2 for early diagnosis and prevention of colorectal cancer. Methods: These biomarkers were analyzed semi-quantified across 231 colonic tissues including 97 adenocarcinomas, 85 adenomas and 49 non-neoplastic colons using immunohistochemistry. In order to differentiate non-neoplastic colons from colorectal neoplasms (adenoma and carcinoma), the values for CYP1B1, AhR, nuclear β-catenin, p53 and bcl-2 expressions were subjected to discrimination analysis, then the cross-validation, sensitivity and specificity of these models were calculated. Results: Expressions of CYP1B1, p53, nuclear β-catenin and bcl-2 were significantly associated with colorectal carcinogenesis (p < 0.01 for the trend test). The overexpression rates for CYP1B1, p53, nuclear β-catenin and bcl-2 were significantly higher in the adenoma and carcinoma groups than in the non-neoplastic colon group (p < 0.05). The discrimination models showed that a combination of two biomarkers was better than a single biomarker, and provided specificity ranging from 39% to 100% and sensitivity ranging from 43% to 82% for colorectal carcinoma. Conclusions: The increase in expression of CYP1B1 occurred not only in colorectal carcinoma and but also in adenoma. Moreover, a screening panel of CYP1B1 in combination with nuclear β-catenin was the most suitable marker pair to screen for colorectal carcinoma based on this study.