Abstract:
Colorectal cancer (CRC) is the most common gastrointestinal malignancy in Malaysia. Progression of the CRC and its invasiveness involve several possible mechanisms such as defects in angiogenesis, cell cycle, Wnt signalling pathway and most recently, by Stat3 signalling pathway. The current study was carried out to evaluate proteins involved in these pathways and to relate their expression with tumour (histological grading and Dukes’ staging) and patient characteristics (ethnicity, age, and gender), with a view to identify potential biomarkers for use in patient management.
A total of 93 CRC specimens were studied histologically using Haematoxylin and Eosin (H&E) staining as well as immunohistochemical staining for vascular endothelial growth factor (VEGF), matrix metalloproteinase 7 (MMP-7), cyclin D1, and cyclin E. A total of 90 specimens were evaluated for CD31 and 80 for -catenin, and 75 for Stat3 and pStat3 expression. The histological findings were correlated with morphological characteristics including tumour differentiation, Dukes’ staging, and patient characteristics.
Positive expression rates for -catenin, VEGF, CD31, cyclin E, MMP-7, Stat3, cyclin D1, and pStat3 were 68.8%, 59.1%, 55.6%, 55.1%, 38.8%, 26.8%, 22.6%, and 13.3% respectively.
Significant association was found between overexpression of VEGF, MMP-7, β-catenin (cytoplasmic and nuclear expression), and Stat3 with the histological grading of CRC. However, no significant association was found between the overexpression of these markers and Dukes’ staging or other patient characteristics. No significant association was found between cyclin E, cyclin D1, pStat3, and CD31 with tumour or patient characteristics.
Co-expression analyses showed that VEGF expression was significantly associated with MMP-7, -catenin, Stat3 and pStat3 (P < 0.05). A positive VEGF has a high positive predictive value of > 85% for β-catenin. Significant association of cyclin D1 was shown for β-catenin, and the positive predictive value of the former for the latter was 90%.
The study has shown that VEGF, MMP-7, β-catenin and Stat3 correlate well with the histological grading but not the staging of CRC. There is a high positive predictive value between VEGF and β-catenin, and also between cyclin D1 and β-catenin. However, -catenin and VEGF have the highest positive expression rates. It is concluded that these two biomarkers would be most useful for evaluating the histological grade of these tumours.
