The clinical significance of SWI/SNF complex in pancreatic cancer.
The clinical significance of SWI/SNF complex in pancreatic cancer.
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DOI：
10.3892/ijo.2012.1723
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发表时间：
2013-02
影响因子：
5.2
通讯作者：
Miyagi Y
中科院分区：
文献类型：
--
作者：
Numata M;Morinaga S;Watanabe T;Tamagawa H;Yamamoto N;Shiozawa M;Nakamura Y;Kameda Y;Okawa S;Rino Y;Akaike M;Masuda M;Miyagi Y
染色质重塑因子一直是肿瘤学研究的热点。然而，人们对它们在胰腺癌中的作用知之甚少。本研究的目的是阐明SWItch/蔗糖非发酵（SWI/SNF）复合物在胰腺癌患者中的临床意义。共入组了68例接受R 0，1切除术的胰腺癌患者。将癌组织处理成组织芯片，然后使用SWI/SNF组分BRM、BRG 1、BAF 250 a、BAF 180和BAF 47的抗体进行化学染色。分析其表达水平与临床病理结果的相关性，并对影响总生存率的预后因素进行多因素分析。SWI/SNF组分的表达水平根据Histosore的中值分为低或高。统计学分析显示BRM表达与肿瘤大小、T因子、M因子、淋巴管浸润有关; BRG 1表达与组织学类型有关; BAF 180表达与肿瘤大小有关; BAF 47表达与淋巴管浸润有关。多因素考克斯比例风险分析显示，BRM高表达和BAF 180低表达是胰腺癌患者生存率较差的独立预测因素。高BRM和低BAF 180也是吉西他滨辅助治疗亚组中生存不良的独立预后因素。这些结果表明，SWI/SNF染色质重塑复合物的特异性辅因子在胰腺癌中肯定有作用。高BRM和低BAF 180是胰腺癌预后不良的有用生物标志物。
Chromatin remodeling factors have been the subject of great interest in oncology. However, little is known about their role in pancreatic cancer. The objective of this study was to clarify the clinical significance of the SWItch/sucrose nonfermentable (SWI/SNF) complex in patients with pancreatic cancer. A total of 68 patients with pancreatic cancer who underwent R0, 1 resection were enrolled. Cancer tissues were processed to tissue microarray, then stained immunohistochemically by using antibody of SWI/SNF components; BRM, BRG1, BAF250a, BAF180 and BAF47. The correlation of expression levels and clinicopathological outcomes were analyzed, followed by the multivariate analysis of prognostic factors for overall survival. The expression levels of the SWI/SNF components were categorized as low or high according to the median value of Histoscore. Statistical analysis revealed that BRM expression was related to tumor size, T factor, M factor, lymphatic invasion and stage BRG1 expression to histology and stage BAF180 expression to tumor size and BAF47 expression to lymphatic invasion, respectively. Multivariate Cox proportional hazard analysis showed that high BRM and low BAF180 expression levels were independent predictors of worse survival in patients with pancreatic cancer. High BRM, and low BAF180 were also independent prognostic factors for poor survival in the subgroup with adjuvant gemcitabine. These results suggest that the specific cofactors of SWI/SNF chromatin remodeling complex certainly have roles in pancreatic cancer. High BRM, and low BAF180 are useful biomarkers for poor prognosis in pancreatic cancer.
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