Using a combination of cytochrome P450 1B1 and beta-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 beta-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 beta-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 beta-catenin and bcl-2 were significantly associated with colorectal carcinogenesis (p<0.01 for the trend test). The overexpression rates for CYP1B1, p53, nuclear beta-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 beta-catenin was the most suitable marker pair to screen for colorectal carcinoma based on this study.
Chang
Han
H
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
Su
Jang-Ming
JM
Huang
Chee C
CC
Liu
Lan C
LC
Tsai
Chung H
CH
Chou
Ming-Chih
MC
Lin
Pinpin
P
D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control; D000236:Adenoma / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000517:prevention & control*; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis; D012680:Sensitivity and Specificity; D013252:Steroid 11-beta-Hydroxylase / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051176:beta Catenin / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D018336:Receptors, Aryl Hydrocarbon; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D013252:Steroid 11-beta-Hydroxylase