Loss of special AT-rich sequence-binding protein 1 (SATB1) predicts poor survival in patients with colorectal cancer
Loss of special AT-rich sequence-binding protein 1 (SATB1) predicts poor survival in patients with colorectal cancer
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DOI：
10.1111/his.12295
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发表时间：
2014-08-01
期刊：
影响因子：
6.4
通讯作者：
Warusavitarne, Janindra
中科院分区：
文献类型：
--
作者：
Al-Sohaily, Sam;Henderson, Christopher;Warusavitarne, Janindra
目的：特殊的AT-Rich序列结合蛋白1(SATB1)是一种细胞类型特异的基质结合区结合蛋白，具有全球基因组组织者的功能。本研究旨在探讨SATB1在结直肠癌中的表达模式及预后价值。方法与结果：收集前瞻性资料，并从352例患者中构建组织芯片。SATB1蛋白的表达采用免疫组织化学方法进行评估，并由两名独立的研究人员进行评分。SATB1在正常组织和癌组织中均以核表达为主。SATB1核表达缺失在结直肠癌中的发生率为22%，而在癌旁正常组织中仅为1.5%，且与患者的总生存率(P=0.02)无关(HR为2.48，95%CI为1.31-4.70)。年龄较小(P=0.03)、粘液或印戒组织学类型的肿瘤(P=0.0001)和分化较差的肿瘤(P=0.005)中SATB-1的表达缺失更为明显。在接受辅助化疗的Dukes C期肿瘤患者中，SATB1的表达与患者的生存优势相关。结论：SATB1核表达缺失与结直肠癌患者的生存和辅助化疗反应差有关。SATB1在结直肠癌个体化治疗中的价值值得进一步评估。
Aim: Special AT-rich sequence-binding protein 1 (SATB1) is a cell type-specific matrix attachment region binding protein, functioning as a global genome organizer. This study aims to investigate the expression pattern and the prognostic value of SATB1 in colorectal cancer.Methods and results: Prospectively collected data were obtained and tissue microarrays were constructed from a cohort of 352 patients. SATB1 protein expression was evaluated by immunohistochemistry and scored by two independent investigators. SATB1 expression was predominantly nuclear in both normal and cancer tissues. Loss of SATB1 nuclear expression was seen in 22% of colorectal cancers compared to 1.5% of adjacent normal colorectal tissue, and was associated with worse overall survival (P = 0.02) independent of age and stage of disease (HR 2.48 with 95% CI 1.31-4.70). Loss of SATB1 expression was more evident in younger patients (P = 0.03), tumours with mucinous or signet ring histology (P = 0.0001) and poor differentiation (P = 0.005). SATB1 expression was associated with a survival advantage in patients with Dukes C tumours who received adjuvant chemotherapy.Conclusion: Loss of SATB1 nuclear expression correlates with poor survival and a less favourable response to adjuvant chemotherapy in colorectal cancer. The value of SATB1 in individualized colorectal cancer therapy warrants further evaluation.