Association of early phase of colorectal carcinogenesis with STAT3 activation and its relevance in apoptosis regulation

Expression of STAT3/pSTAT3 in colorectal cancer (CRC) patients of Indian origin was studied to assess its significance in early detection and apoptosis regulation. Colorectal tissues with malignant lesions were STAT3/pSTAT3 positive in 66% of the cases and among these positive cases, well differentiated, moderately differentiated and poorly differentiated cancers were 86%, 60% and 0% respectively. All CRC specimens studied were immunoreactive with anti-carcinoembryonic antigen antibody. Cells purified from CRC tissues exhibited greater STAT3/pSTAT3 reactivity than peripheral blood mononuclear cells (PBMC) from healthy individuals, which served as control. apoptotic index (AI) was comparatively low in tissue specimens with STAT3/pSTAT3 expression. CRC cells with a comparatively less number of apoptotic cells, expressed a minimum number of Caspase-3 positive cells (4.73%), in comparison to healthy-PBMC (12.63%). CRC cells with high STAT3/pSTAT3 staining had cells with greater percentage of Bcl2 reactivity (23.05%), but less positivity with Caspase3 antibody (2.05%). Overall data suggests that CRC population was STAT3/pSTAT3 immunoreactive in a stage specific manner and STAT3 protects cancerous colorectal epithelial cells from apoptosis. Bcl-2, Cyclin D1 and Caspase-3 control the activity of apoptosis regulator, STAT3.