YAP1和pSTAT3-S727在胶质瘤中的表达及其预后价值。

Expression of YAP1 and pSTAT3-S727 and their prognostic value in glioma.

作者信息

Sang Wei, Xue Jing, Su Li-Ping, Gulinar Abulajiang, Wang Qian, Zhai Yang-Yang, Hu Yan-Ran, Gao Hai-Xia, Li Xinxia, Li Qiao-Xing, Zhang Wei

机构信息

Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.

Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China

出版信息

J Clin Pathol. 2021 Aug;74(8):513-521. doi: 10.1136/jclinpath-2020-206868. Epub 2020 Oct 5.

DOI:10.1136/jclinpath-2020-206868

PMID:33020176

Abstract

AIMS

A growing research demonstrated that YAP1 played important roles in gliomagenesis. We explored the expression of YAP1 and STAT3, the relationship between them and the effect of YAP1, STAT3 on prognosis in glioma.

METHODS

Expression of YAP1, p-YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 in 141 cases of low-grade gliomas (LGG) and 74 cases of high-grade gliomas (HGG) of surgical specimens were measured by immunohistochemistry. Pearson's X test was used to determine the correlation between immunohistochemical expressions and clinicopathological parameters. Pearson's or Spearman correlation test was used to determine the association between these proteins expression. Survival analysis was used to investigate the effect of these proteins on prognosis.

RESULTS

High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in HGG compared with LGG (p=0.000). High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in 63.5%, 59.5%, 66.2% and 31.1% cases of HGG, respectively. YAP1 expression was associated to tumour location, Ki-67 and P53, STAT3 expression was related with Ki-67 and P53, and the expression of pSTAT3-S727 was associated with Ki-67. There was a significantly positive correlation between YAP1 and pSTAT3-S727 (p<0.0001; r=0.5663). Survival analysis revealed that patients with YAP1 and pSTAT3-S727 coexpression had worse overall survival (OS) and progression-free survival (PFS) (p<0.0001). Tumour grade, age, Ki-67 and YAP1 expression were independent prognostic factors for OS. In LGG group, both YAP1 and pSTAT3-S727 expressions were negative correlation with IDH1 mutation, YAP1 and pSTAT3-S727 coexpression showed worse OS and PFS of glioma patients.

CONCLUSION

Our research showed that YAP1 and STAT3 were significantly activated in HGG compared with LGG. YAP1 significantly correlated with pSTAT3-S727 in glioma, YAP1 and pSTAT3-S727 coexpression may serve as a reliable prognostic biomarker and therapeutic target for glioma.

摘要

目的

越来越多的研究表明YAP1在胶质瘤发生过程中发挥重要作用。我们探讨了YAP1和STAT3的表达、它们之间的关系以及YAP1、STAT3对胶质瘤预后的影响。

方法

采用免疫组织化学法检测141例低级别胶质瘤（LGG）和74例高级别胶质瘤（HGG）手术标本中YAP1、p-YAP1、STAT3、pSTAT3-S727和pSTAT3-Y705的表达。采用Pearson卡方检验确定免疫组化表达与临床病理参数之间的相关性。采用Pearson或Spearman相关检验确定这些蛋白表达之间的关联。采用生存分析研究这些蛋白对预后的影响。

结果

与LGG相比，HGG中YAP1、STAT3、pSTAT3-S727和pSTAT3-Y705的表达较高（p = 0.000）。在HGG病例中，YAP1、STAT3、pSTAT3-S727和pSTAT3-Y705的高表达分别见于63.5%、59.5%、66.2%和31.1%的病例。YAP1表达与肿瘤位置、Ki-67和P53相关，STAT3表达与Ki-67和P53相关，pSTAT3-S727的表达与Ki-67相关。YAP1与pSTAT3-S727之间存在显著正相关（p < 0.0001；r = 0.5663）。生存分析显示，YAP1和pSTAT3-S727共表达的患者总生存期（OS）和无进展生存期（PFS）较差（p < 0.0001）。肿瘤分级、年龄、Ki-67和YAP1表达是OS的独立预后因素。在LGG组中，YAP1和pSTAT3-S727的表达均与IDH1突变呈负相关，YAP1和pSTAT3-S727共表达显示胶质瘤患者的OS和PFS较差。