Overexpression of SOX 9 and DNMT 1 predicts poor prognosis and chemoresistance of colorectal cancer

Colorectal cancer is one of the most leading causes of cancer-related death. Epithelial-mesenchymal transition (EMT) is integral in cancer stem cell behavior, and contributes pathologically to cancer progression. Both SOX9 and DNMT1 have predominant roles in EMT. The purpose of this study is to determine the expression pattern and clinical relevance of SOX9 and DNMT1 in human CRC. Immunohistochemical staining showed that SOX9 and DNMT1 overactivated in CRC (P<0.001, P<0.001). SOX9 (hi) expression was positively associated with histological classification of CRC patients (P=0.001). DNMT1 (hi) expression was significantly associated with histological classification (P<0.001), LN stages (P<0.001) and TNM stages (P=0.001) of CRC patients. SOX9 expression was positively correlated with DNMT1 expression (ρ=0.540, P<0.001). SOX9 (hi) DNMT1 (hi) expression was positively associated with histological classification (P=0.003), LN stages (P=0.018) and TNM stages (P=0.004) of CRC patients. In 184 patients with survival information, both SOX9 (hi) and DNMT1 (hi) expressions were associated with unfavorable prognosis (P<0.001, P<0.001). SOX9 (hi) DNMT1 (hi) expression patient shown much poorer prognosis (P<0.001). Cox regression analysis showed that histological classification, LN stage, SOX9 (hi) expression, DNMT1 (hi) expression and double (hi) expression of SOX9 and DNMT1 were independent prognostic factors. This study provides the first evidence that SOX9 and DNMT1 are both relevant to malignant characteristics of CRC. Our data suggests the potential of SOX9 and DNMT1 as prognostic biomarkers for CRC and predictive marker of FOLFOX regimens.