P38 MAPK expression and activation predicts failure of response to CHOP in patients with Diffuse Large B-Cell Lymphoma.
P38 MAPK expression and activation predicts failure of response to CHOP in patients with Diffuse Large B-Cell Lymphoma.
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DOI：
10.1186/s12885-015-1778-8
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发表时间：
2015-10-16
期刊：
影响因子：
3.8
通讯作者：
Vega MI
中科院分区：
文献类型：
--
作者：
Vega GG;Avilés-Salas A;Chalapud JR;Martinez-Paniagua M;Pelayo R;Mayani H;Hernandez-Pando R;Martinez-Maza O;Huerta-Yepez S;Bonavida B;Vega MI
p38 MAPK在B-NHL细胞系中组成性激活并调节化学耐药。因此，我们假设活化的p38 MAPK可能与B-NHL患者体内对化疗无反应有关。采用免疫组织化学方法检测80例未经治疗的弥漫性大B细胞淋巴瘤（DLBCL）患者的组织微阵列中p38和磷酸p38 (p-p38) MAPK的表达。同时检测Bcl-2和NF-κB的表达。Kaplan Meier分析进行评估。肿瘤组织表达p38 MAPK（82%）和p-p38 MAPK（30%）。p38和p-p38 MAPK表达均与高分成绩状态相关。p-p38的表达与CHOP不良反应之间存在显著相关性。p38 -组5年随访中位FFS为81%，p38+组为34%，p38 -组为83%，p38+组为47%。p-p38+组织表达Bcl-2和90%的p-p38−，其中Bcl-2−。p-p38和Bcl-2的共表达与池EFS和OS相关。p-p38的表达与NF-κB的表达无相关性。研究结果首次显示，一部分肿瘤表达高p-p38 MAPK的DLBCL患者对CHOP治疗反应较差，EFS和OS较差。p38、p-p38、Bcl2和ABC亚型的表达是重要的危险因素，p38和p-p38的表达仍然是独立的预后因素。本文的在线版本（doi:10.1186/s12885-015-1778-8）包含补充材料，授权用户可以使用。
The p38 MAPK is constitutively activated in B-NHL cell lines and regulates chemoresistance. Accordingly, we hypothesized that activated p38 MAPK may be associated with the in vivo unresponsiveness to chemotherapy in B-NHL patients. Tissue microarrays generated from eighty untreated patients with Diffused Large B Cell Lymphoma (DLBCL) were examined by immunohistochemistry for the expression of p38 and phospho p38 (p-p38) MAPK. In addition, both Bcl-2 and NF-κB expressions were determined. Kaplan Meier analysis was assessed. Tumor tissues expressed p38 MAPK (82 %) and p-p38 MAPK (30 %). Both p38 and p-p38 MAPK expressions correlated with the high score performance status. A significant correlation was found between the expression p-p38 and poor response to CHOP. The five year median follow-up FFS was 81 % for p38− and 34 % for p38+ and for OS was 83 % for p38− and 47 % for p38+. The p-p38+ tissues expressed Bcl-2 and 90 % of p-p38− where Bcl-2−. The coexpression of p-p38 and Bcl-2 correlated with pool EFS and OS. There was no correlation between the expression of p-p38 and the expression of NF-κB. The findings revealed, for the first time, that a subset of patients with DLBCL and whose tumors expressed high p-p38 MAPK responded poorly to CHOP therapy and had poor EFS and OS. The expression of p38, p-p38, Bcl2 and the ABC subtype are significant risk factors both p38 and p-p38 expressions remain independent prognostic factors. The online version of this article (doi:10.1186/s12885-015-1778-8) contains supplementary material, which is available to authorized users.