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CDKL2 与胃癌的 HER2 状态和总生存期相关:CDKL2 蛋白表达和基因拷贝数的比较分析。

CDKL2 Is Associated with HER2 Status and Overall Survival in Gastric Cancer: Comparative Analysis of CDKL2 Protein Expression and Gene Copy Number.

机构信息

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

出版信息

Biomed Res Int. 2020 Oct 31;2020:1712723. doi: 10.1155/2020/1712723. eCollection 2020.

Abstract

BACKGROUND

Cyclin-dependent kinase-like 2 (CDKL2) is a member of the CDKL family and recognized as a novel regulator of epithelial-mesenchymal transition of breast cancer cells, but its role has not been explored in gastric cancer (GC). This study was to characterize the CDKL2 protein expression and gene copy number in relation to human epidermal growth factor receptor 2 (HER2) status, clinicopathological features, and overall survival (OS) in GC.

METHODS

This study detected the CDKL2 protein expression and gene copy number by immunochemistry (IHC) and fluorescent in situ hybridization (FISH), respectively, in 334 GC samples. HER2 status was determined according to established criteria. Associations of the CDKL2 protein expression and gene copy number with OS in GC were evaluated, and the association between CDKL2 mRNA expression and OS in GC was also analyzed using TCGA data.

RESULTS

The detection results suggested that 34.1% cases showed high CDKL2 protein expression; 11.4% cases had ≥5 copies of CDKL2 gene or a ratio of CDKL2 to chromosome of ≥2. The CDKL2 protein expression was markedly correlated with its gene copy number. High protein expression and high gene copy number were both significantly associated with positive HER2 status, and they both could predicted a shorter OS, although not as independent markers suggested by the multivariate Cox proportional hazard regression analysis. The TCGA data indicated that higher CDKL2 mRNA level also predicted a shorter OS in GC.

CONCLUSIONS

The combined detection of the CDKL2 protein level and gene copy number could be of important value in predicting HER2 status and prognosis of patients with GC.

摘要

背景

周期素依赖性激酶样 2(CDKL2)是 CDKL 家族的成员,被认为是乳腺癌细胞上皮-间质转化的新型调节因子,但在胃癌(GC)中其作用尚未得到探索。本研究旨在探讨 CDKL2 蛋白表达和基因拷贝数与人类表皮生长因子受体 2(HER2)状态、临床病理特征和总生存(OS)的关系。

方法

本研究通过免疫组织化学(IHC)和荧光原位杂交(FISH)分别检测了 334 例 GC 样本中的 CDKL2 蛋白表达和基因拷贝数。HER2 状态根据既定标准确定。评估了 CDKL2 蛋白表达与 GC 患者 OS 的相关性,同时使用 TCGA 数据分析了 CDKL2 mRNA 表达与 GC 患者 OS 的相关性。

结果

检测结果表明,34.1%的病例表现出高 CDKL2 蛋白表达;11.4%的病例存在 CDKL2 基因≥5 个拷贝数或 CDKL2 与染色体的比值≥2。CDKL2 蛋白表达与基因拷贝数显著相关。高蛋白表达和高基因拷贝数均与阳性 HER2 状态显著相关,尽管多变量 Cox 比例风险回归分析并未将其作为独立标志物,但均能预测 OS 较短。TCGA 数据表明,GC 中较高的 CDKL2 mRNA 水平也预示着较短的 OS。

结论

联合检测 CDKL2 蛋白水平和基因拷贝数可能对预测 GC 患者的 HER2 状态和预后具有重要价值。

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