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HDAC7在胃癌组织中的表达与远处转移及患者预后不良呈正相关。

The expression of HDAC7 in cancerous gastric tissues is positively associated with distant metastasis and poor patient prognosis.

作者信息

Yu Y, Cao F, Yu X, Zhou P, Di Q, Lei J, Tai Y, Wu H, Li X, Wang X, Zhang W, Li P, Li Y

机构信息

Department of Oncology, Renmin Hospital, Hubei University of Medicine, 39 Chaoyang Rd., 442000, Shiyan, China.

Department of Medical Laborotary, The First Affiliated Hospital, Nanchang University, 330006, Nanchang, China.

出版信息

Clin Transl Oncol. 2017 Aug;19(8):1045-1054. doi: 10.1007/s12094-017-1639-9. Epub 2017 Mar 15.

Abstract

PURPOSE

To characterize the expression patterns of HDAC7 in patients with gastric cancer and evaluate the prognostic value of HDAC7 in gastric cancer.

METHODS

The expression of histone deacetylase 7 (HDAC7) was detected in paraffin-embedded gastric cancer samples from 86 patients by immunohistochemistry, and the differences in the expression of HDAC7 between cancerous and corresponding adjacent noncancerous tissues were compared using the Wilcoxon matched-pairs signed rank test. The correlation between HDAC7 expression and Ki-67 expression or clinicopathologic characteristics was evaluated using a Spearman rank correlation test. Prognostic outcomes that correlated with HDAC7 were examined using a Kaplan-Meier analysis and Cox proportional hazards model. Moreover, the effects of HDAC7 on the proliferation, migration and invasion of gastric cancer cells were investigated in vitro using human gastric carcinoma AGS cells.

RESULTS

We found that HDAC7 was downregulated in cancerous gastric tissues (P = 0.0019). However, the expression of HDAC7 in cancerous gastric tissues positively correlated with Ki-67 expression (P = 0.0325) and distant metastasis (P = 0.020). Moreover, overall survival was shorter for patients expressing higher levels of HDAC7 in cancerous tissues (P = 0.042). Mechanistically, the disruption of the HDAC7 gene attenuated the capacity of cell growth, migration and invasion and induced G0/G1 arrest in AGS cells. Conversely, forced ovperexpression of HDAC7 promoted cell growth, migration and invasion and G1/S transition in AGS cells.

CONCLUSIONS

These results indicate that high HDAC7 expression in cancerous gastric tissues correlates with distant metastasis and predicts a poor prognosis for patients with gastric cancer.

摘要

目的

明确胃癌患者中组蛋白去乙酰化酶7(HDAC7)的表达模式,并评估HDAC7在胃癌中的预后价值。

方法

采用免疫组织化学法检测86例患者石蜡包埋胃癌样本中组蛋白去乙酰化酶7(HDAC7)的表达,使用Wilcoxon配对符号秩和检验比较癌组织与相应癌旁非癌组织中HDAC7表达的差异。采用Spearman秩相关检验评估HDAC7表达与Ki-67表达或临床病理特征之间的相关性。使用Kaplan-Meier分析和Cox比例风险模型检查与HDAC7相关的预后结果。此外,体外用人胃癌AGS细胞研究HDAC7对胃癌细胞增殖、迁移和侵袭的影响。

结果

我们发现HDAC7在胃癌组织中表达下调(P = 0.0019)。然而,HDAC7在胃癌组织中的表达与Ki-67表达(P = 0.0325)和远处转移(P = 0.020)呈正相关。此外,癌组织中HDAC7表达水平较高的患者总生存期较短(P = 0.042)。机制上看,HDAC7基因的破坏减弱了AGS细胞的生长、迁移和侵袭能力,并诱导G0/G1期阻滞。相反,HDAC7的强制过表达促进了AGS细胞的生长、迁移和侵袭以及G1/S期转换。

结论

这些结果表明,胃癌组织中HDAC7的高表达与远处转移相关,并预示着胃癌患者的预后不良。

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