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CCND1 诱导的自噬有助于子宫内膜癌的淋巴结转移。

CCND1-Induced Autophagy Contributes to Lymph Node Metastasis in Endometrial Cancer.

机构信息

Shandong University Cancer Center, Jinan, China.

Department of Radiotherapy, Yantai Yuhuangding Hospital, Yantai, China.

出版信息

Horm Metab Res. 2023 Jun;55(6):413-419. doi: 10.1055/a-2044-9227. Epub 2023 Apr 5.

DOI:10.1055/a-2044-9227
PMID:37019147
Abstract

Endometrial cancer with lymph node metastasis shows poor prognosis, while the biomarker to predict the metastasis is lacking. The relative mRNA or protein expression of cyclin D1 (CCND1) and autophagy-related molecules were detected in real-time PCR and Western blot. Correlation analysis was applied to identify any significant patterns, and receiver operating characteristics (ROC) was performed to assess the prediction value. CCND1 vector was transfected in Ishikawa (ISK) cells, and the relative expression of autophagy-related molecules was detected with Western blot. CCND1 was overexpressed in endometrial cancer and correlated with lymph node metastasis. ROC analysis found that CCND1 had a predictive value to discriminate tumors from normal tissues (cut off=1.455; sensitivity, 71%; specificity, 84%; area under curve (AUC) 0.82; p<0.001) and had a predictive value to indicate metastasis (cut off=1.871; sensitivity, 54.17%; specificity, 75%; AUC 0.674; p=0.003). Increased BECLIN1 (r=0.39, p<0.001) and ATG5 (r=0.41, p<0.001) expression were positively correlated to CCND1. On the other hand, the relative protein expression of CCND1, BECLIN1, ATG5, ATG7, and LC3 I/II were also increased in tumor tissues. CCND1 overexpressed ISK cells showed upregulated BECLIN1, ATG5, ATG7, and LC3 I/II expression. CCND1 promoted autophagy may contribute to lymph node metastasis in endometrial cancer.

摘要

子宫内膜癌伴淋巴结转移预后不良,而预测转移的生物标志物尚缺乏。采用实时 PCR 和 Western blot 检测细胞周期蛋白 D1 (CCND1) 和自噬相关分子的相对 mRNA 或蛋白表达。应用相关性分析来确定任何显著模式,并进行接收者操作特征 (ROC) 分析以评估预测价值。在 Ishikawa (ISK) 细胞中转染 CCND1 载体,并用 Western blot 检测自噬相关分子的相对表达。CCND1 在子宫内膜癌中过表达,并与淋巴结转移相关。ROC 分析发现,CCND1 具有区分肿瘤与正常组织的预测价值 (截断值=1.455;灵敏度,71%;特异性,84%;曲线下面积 (AUC) 0.82;p<0.001),并且具有指示转移的预测价值 (截断值=1.871;灵敏度,54.17%;特异性,75%;AUC 0.674;p=0.003)。BECLIN1(r=0.39,p<0.001)和 ATG5(r=0.41,p<0.001)表达的增加与 CCND1 呈正相关。另一方面,肿瘤组织中 CCND1、BECLIN1、ATG5、ATG7 和 LC3 I/II 的相对蛋白表达也增加。过表达 CCND1 的 ISK 细胞显示 BECLIN1、ATG5、ATG7 和 LC3 I/II 表达上调。CCND1 促进自噬可能有助于子宫内膜癌的淋巴结转移。

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