Low expression of CysLT1R and high expression of CysLT2R mediate good prognosis in colorectal cancer.
Colorectal cancer is the third most common cancer type in the Western world. In search of new treatment possibilities, the inflammation mediators, know as cysteinyl leukotrienes (CysLTs), have been shown to regulate intestinal epithelial cell survival and proliferation via the CysLT(1)R, and cell differentiation via the CysLT(2)R. These results prompted us to investigate the significance of CysLT(1)R and CysLT(2)R expression in colorectal cancer tissue for patient survival. The CysLT(1)R, CysLT(2)R, beta-catenin and Bcl-xL protein expression levels were evaluated by immunohistochemistry in a tissue microarray of 329 colorectal patients. We found that high nuclear expression of CysLT(1)R is associated with a poor prognosis, whereas high nuclear expression of CysLT(2)R is associated with a good prognosis. We also observed that patients with colorectal tumours characterised by high CysLT(1)R but low CysLT(2)R nuclear expression had the lowest survival expectancy, whereas patients with colorectal tumours characterised by low CysLT(1)R but high CysLT(2)R nuclear expression had the best survival expectancy. Interestingly, beta-catenin as a single prognostic marker did not exhibit any prognostic value. However, in patients with tumours characterised by a high CysLT(1)R nuclear expression, an elevated beta-catenin nuclear expression had a significantly prognostic value. In conclusion these data indicate that nuclear expressions of CysLTRs are potential prognostic indicators of colorectal cancer.
Magnusson
Cecilia
C
Cell and Experimental Pathology, Department of Laboratory Medicine, Sweden.
Mezhybovska
Maryna
M
Lörinc
Ester
E
Fernebro
Eva
E
Nilbert
Mef
M
Sjölander
Anita
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D003600:Cytosol / Q000378:metabolism; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D011379:Prognosis; D018077:Receptors, Leukotriene / Q000378:metabolism*; D046888:Tissue Array Analysis / Q000379:methods; D051176:beta Catenin / Q000378:metabolism
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D009363:Neoplasm Proteins; D018077:Receptors, Leukotriene; D051176:beta Catenin; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor