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HDAC8的过表达下调CDKN2A与食管鳞状细胞癌的预后较差相关。

Over-expression of HDAC8 down-regulate CDKN2A is associated with worse prognosis of esophageal squamous cell carcinoma.

作者信息

Nesa Effat Un, Chen Xuan, Wang Cong, Chen Xue, Wang Yuan, Qu Yan, Mi Si, Guan Shanghai, Xiao Fengxia, Cheng Yufeng

机构信息

Department of Radiation Oncology, Qilu Hospital of Shandong University, Ji'nan 250012, China.

Department of Radiation Oncology, Linyi People's Hospital, Linyi 276003, China.

出版信息

Transl Cancer Res. 2020 Mar;9(3):1406-1417. doi: 10.21037/tcr.2020.01.32.

Abstract

BACKGROUND

The epigenetic alteration has an impact on cancer cell cycle regulation. Expression of histone deacetylase 8 (HDAC8) ruled out the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A) and this is linked with the prognosis of Esophageal cancer (EC) patients.

METHODS

By the immunohistochemical staining, we examined the expression status of HDAC8 and CDKN2A protein of 110 esophageal squamous cell carcinoma (ESCC) patients in the tissue microarray. The nuclear staining intensity was counted by immunoreactivity scoring ranging from 0 to 12 and grouped them into two; weak or non-expression and over-expression.

RESULTS

The median follow-up duration of our study was 71 months postoperatively. Up-regulation of HDAC8 expression and down-regulation of CDKN2A (p16) indicate decreased 5-year overall survival (OS) (P=0.003) and (P=0.001) respectively and progression-free survival (PFS) (P=0.005, P=0.001) respectively, which are statistically significant and determined by Kaplan-Meier estimates using log-rank test. Consequently, HDAC8 and CDKN2A act as an independent prognostic biomarker, for OS and PFS that analyzed by multivariate cox-regression analysis, HR 1.173 with 95% CI: 0.215-6.416 and P=0.003 and HR 1.217 with 95% CI: 0.224-6.600 and P=0.005 respectively. Spearman rank test establish the negative correlation between HDAC8 and CDKN2A.

CONCLUSIONS

Over-expression of HDAC8 and weak or no expression of CDKN2A have a worse impact on EC patients and indicate poor survival and progression of the disease and act as a promising prognostic parameter.

摘要

背景

表观遗传改变对癌细胞周期调控有影响。组蛋白去乙酰化酶8(HDAC8)的表达排除了细胞周期蛋白依赖性激酶抑制剂2A(CDKN2A)的表达,这与食管癌(EC)患者的预后相关。

方法

通过免疫组织化学染色,我们检测了组织芯片中110例食管鳞状细胞癌(ESCC)患者HDAC8和CDKN2A蛋白的表达状态。通过免疫反应评分将细胞核染色强度计为0至12,并将其分为两组;弱表达或无表达以及过表达。

结果

我们研究的中位随访时间为术后71个月。HDAC8表达上调和CDKN2A(p16)表达下调分别表明5年总生存期(OS)降低(P = 0.003)和(P = 0.001),无进展生存期(PFS)分别降低(P = 0.005,P = 0.001),这具有统计学意义,通过使用对数秩检验的Kaplan-Meier估计确定。因此,HDAC8和CDKN2A作为独立的预后生物标志物,通过多变量cox回归分析分析OS和PFS,HR分别为1.173,95% CI:0.215 - 6.416,P = 0.003和HR为1.217,95% CI:0.224 - 6.600,P = 0.005。Spearman秩检验确定HDAC8与CDKN2A之间存在负相关。

结论

HDAC8过表达和CDKN2A弱表达或无表达对EC患者有更坏的影响,表明疾病的生存期和进展较差,并作为一个有前景的预后参数。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ec7/8798431/f733e1b3ede7/tcr-09-03-1406-f1.jpg

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