SATB1在直肠癌新辅助放疗中的作用

Role of SATB1 in neoadjuvant radiotherapy of rectal cancer

目的探讨SATB1在直肠癌新辅助放疗中的作用。方法选取142例直肠癌患者作为研究对象,其中68例接受术前短程放疗,74例未接受术前放疗。采用组织芯片方法检测直肠癌组织(n=142)和正常黏膜组织(n=107)、术前活检癌组织(n=84)以及转移淋巴结(n=43)中SATB1表达情况,探讨SATB1表达对直肠癌患者预后的影响,并通过生物信息学方法分析SATB1表达与多个放疗相关因子的关系。结果在未接受术前放疗的患者中,SATB1在正需组织中的表达低于肿瘤组织(X^2=5.396,P=0.032)而肿瘤组织中的表达高于淋巴结转移组织(X^2=6.405,P=0.002)。在接受术前放疗的患者中,SATB1表达与不良的OS(HR,0.516;P=0.039;95%CI:0.274～0.969)和DFS(HR,0.558;P=0.025;95%CI:0.335～0.930)相关。放疗可以降低直肠癌组织中SATB1的表达。在放疗的直肠癌肿瘤组织中SATB1表达与ATM和pRb2/p130表达负相关(X^2=5.427,P=0.032;X^2=4.610, P=0.047),而与Ki-67和TEM1表达正相关(X^2=4.339,P=0.037;X^2=7.376,P=0.014)。网络和蛋白-蛋白相互作用分析证实了SATB1与这些蛋白的相互联系。结论放疗能降低SATB1表达,后者可通过参与一些放疗反应相关的信号通路,赋予接受术前放疗的直肠癌患者生存获益。

ObjectiveTo investigate the role of special AT-rich sequence binding protein 1 （SATB1） in neoadjuvant radiotherapy of rectal cancer. MethodsSATB1 expression was immunohistochemically determined in primary cancer, normal mucosa, biopsy and lymph node metastasis from 142 rectal cancer patients who underwent preoperative radiotherapy （RT）, 68 with and 74 without RT before surgery. The expression of SATB1 in rectal cancer tissues （n=142） and normal mucosa tissues （n=107）, preoperative biopsy cancer tissues （n=84）, and metastatic lymph nodes （n=43） were detected by tissue microarray. To investigate the effect of SATB1 expression on the prognosis of patients with rectal cancer. The relationship between SATB1 expression and multiple radiotherapy-related factors was analyzed by bioinformatics methods. ResultsSATB1 increased from normal mucosa to primary cancer （χ2=5.396, P=0.032）, whereas it decreased from primary cancer to lymph node metastasis （χ2=6.405, P=0.022） in non-RT patients. Strong SATB1 was independently related to worse overall survival （HR, 0.516; P=0.039; 95% CI： 0.274~0.969） and disease-free survival （HR, 0.558; P=0.025; 95% CI： 0.335~0.930） in RT but not non-RT patients. Radiation can decrease SATB1 expression of rectal cancer tissues. SATB1 was negatively related to ataxiatelangiectasia mutated （ATM） and pRb2/p130 （χ2=5.427, P=0.032 and χ2=4.610, P=0.047）, and positively to Ki-67 and TEM1 expression （χ2=4.339, P=0.037 and χ2=7.376, P=0.014） in patients underwent surgery after preoperative RT, which were verified in bioinformatics analysis. ConclusionsRadiation can decrease SATB1 expression, and SATB1 may confer survival benefit for rectal cancer patients with preoperative RT by involving in radiation-responsive signaling pathways.