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膜联蛋白A7在晚期胃癌中表达下调,且与分化程度和凋亡率呈负相关。

Annexin A7 expression is downregulated in late-stage gastric cancer and is negatively correlated with the differentiation grade and apoptosis rate.

作者信息

Ye Weihua, Li Yong, Fan Liqiao, Zhao Qun, Yuan Hufang, Tan Bibo, Zhang Zhidong

机构信息

Department of Ultrasound, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

出版信息

Oncol Lett. 2018 Jun;15(6):9836-9844. doi: 10.3892/ol.2018.8576. Epub 2018 Apr 25.

Abstract

Annexin A7 is a member of the Annexin A family, which participates in various biological processes. Accumulating evidence has demonstrated that Annexin A7 serves an important role in tumorigenesis and is dysregulated in multiple types of cancer. However, the role of Annexin A7 in the tumorigenesis of gastric cancer remains to be determined. The present study revealed that Annexin A7 expression is downregulated in late-stage gastric cancer and is negatively correlated with the differentiation grade and apoptosis. There was a significant difference in Annexin A7 mRNA and protein expression in gastric cancer samples with distinct differentiation grades, with the lowest expression being observed in the highly differentiated cases. A terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling assay demonstrated that the apoptosis indices of highly, moderately and poorly differentiated gastric cancers were 18.12±2.40, 9.73±1.73 and 4.13±0.83%, respectively, with statistical significance (P<0.05). Flow cytometric analysis demonstrated that the apoptosis rates of gastric cancer MKN74, SGC7901 and BGC823 cells were 10.07±1.21, 7.11±1.04 and 4.25±1.02%, respectively, with statistical significance (P<0.05). Spearman's rank correlation analysis revealed that the Annexin A7 mRNA and protein levels were negatively correlated with the differentiation grade of the gastric cancer tissues, while the apoptosis index was positively correlated with the differentiation grade of the gastric cancer tissues. Furthermore, the apoptosis index was negatively correlated with Annexin A7 mRNA and protein expression. Similar associations were observed among Annexin A7 expression, differentiation grades and apoptosis in gastric cancer cell lines. The results of the present study demonstrated that Annexin A7 expression is downregulated, while apoptosis is upregulated, with the progression of gastric adenocarcinoma. These observations suggested that Annexin A7 may inhibit apoptosis during tumorigenesis and that it is a potential biomarker for the diagnosis, prognosis and treatment of gastric adenocarcinoma.

摘要

膜联蛋白A7是膜联蛋白A家族的成员之一,参与多种生物学过程。越来越多的证据表明,膜联蛋白A7在肿瘤发生中起重要作用,并且在多种类型的癌症中表达失调。然而,膜联蛋白A7在胃癌发生中的作用仍有待确定。本研究表明,膜联蛋白A7在晚期胃癌中表达下调,且与分化程度和细胞凋亡呈负相关。在不同分化程度的胃癌样本中,膜联蛋白A7 mRNA和蛋白表达存在显著差异,在高分化病例中表达最低。末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法显示,高分化、中分化和低分化胃癌的凋亡指数分别为18.12±2.40%、9.73±1.73%和4.13±0.83%,具有统计学意义(P<0.05)。流式细胞术分析显示,胃癌MKN74、SGC7901和BGC823细胞的凋亡率分别为10.07±1.21%、7.11±1.04%和4.25±1.02%,具有统计学意义(P<0.05)。Spearman等级相关分析显示,膜联蛋白A7 mRNA和蛋白水平与胃癌组织的分化程度呈负相关,而凋亡指数与胃癌组织的分化程度呈正相关。此外,凋亡指数与膜联蛋白A7 mRNA和蛋白表达呈负相关。在胃癌细胞系中,膜联蛋白A7表达、分化程度和细胞凋亡之间也观察到类似的关联。本研究结果表明,随着胃腺癌的进展,膜联蛋白A7表达下调,而细胞凋亡上调。这些观察结果提示,膜联蛋白A7可能在肿瘤发生过程中抑制细胞凋亡,并且它是胃腺癌诊断、预后和治疗的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a3b/6004673/37996cc7c67d/ol-15-06-9836-g00.jpg

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