Overexpression of SOX 9 and DNMT 1 predicts poor prognosis and chemoresistance of colorectal cancer
Overexpression of SOX 9 and DNMT 1 predicts poor prognosis and chemoresistance of colorectal cancer
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发表时间：
2016
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通讯作者：
S. Xia;Zhaojuan Yang;X. Qi;Y. Pu;Yankui Liu;Boshi Wang;Yun Liu;Li Zhang;Yu Qian;A. Ma;Guiqin Xu;H. Tu;Yongzhong Liu
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作者：
S. Xia;Zhaojuan Yang;X. Qi;Y. Pu;Yankui Liu;Boshi Wang;Yun Liu;Li Zhang;Yu Qian;A. Ma;Guiqin Xu;H. Tu;Yongzhong Liu
结直肠癌是癌症相关死亡的最主要原因之一。上皮-间质转化（EMT）是癌症干细胞行为中不可或缺的一部分，并在病理学上有助于癌症进展。SOX 9和DNMT 1在EMT中均起主导作用。本研究的目的是确定SOX 9和DNMT 1在人CRC中的表达模式和临床相关性。免疫组化染色显示SOX 9和DNMT 1在大肠癌中过度表达（P<0.001，P<0.001）。SOX 9（hi）表达与大肠癌组织学分型呈正相关（P=0.001）。DNMT 1（hi）表达与结直肠癌组织学分型（P<0.001）、LN分期（P<0.001）和TNM分期（P=0.001）有关。SOX 9与DNMT 1表达呈正相关（ρ=0.540，P<0.001）。SOX 9（hi）和DNMT 1（hi）的表达与结直肠癌组织学类型（P=0.003）、LN分期（P=0.018）和TNM分期（P=0.004）呈正相关。在184例有生存信息的患者中，SOX 9（hi）和DNMT 1（hi）表达均与预后不良有关（P<0.001，P<0.001）。SOX 9（hi）和DNMT 1（hi）阳性表达者预后差（P<0.001）。考克斯回归分析显示，组织学分型、LN分期、SOX 9（hi）表达、DNMT 1（hi）表达及SOX 9和DNMT 1双表达是影响预后的独立因素。这项研究首次证明了SOX 9和DNMT 1都与CRC的恶性特征相关。我们的数据表明SOX 9和DNMT 1作为CRC的预后生物标志物和FOLFOX方案的预测标志物的潜力。
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.