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PLS3 预测胰腺癌预后不良,并通过 PI3K/AKT 信号通路促进癌细胞增殖。

PLS3 predicts poor prognosis in pancreatic cancer and promotes cancer cell proliferation via PI3K/AKT signaling.

机构信息

Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China.

Department of Hepatobiliary and Pancreatic Surgery, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, China.

出版信息

J Cell Physiol. 2020 Nov;235(11):8416-8423. doi: 10.1002/jcp.29685. Epub 2020 Apr 2.

DOI:10.1002/jcp.29685
PMID:32239705
Abstract

Plastin-3 plays a key role in cancer cell proliferation and invasion, but its prognostic value in pancreatic cancer (PACA) remains poorly defined. In this study, we show that PLS3 messenger RNA is overexpressed in PACA tissue compared with normal tissue. We accumulated 207 cases of PACA specimens to perform immunohistochemical analysis and demonstrated that PLS3 levels correlate with T-classification (p < .001) and pathology (p < .001). Furthermore, overall survival rates (p < .001) in tumors with high PLS3 expression were poor, as assessed through Kaplan-Meier survival analysis. PLS3 was found to be an independent prognostic factor for PACA through multivariate Cox regression analysis. Moreover, we found that PLS3 enhances the proliferation and invasion of tumor cells as assessed through Cell Counting Kit-8, wounding healing assays, and Transwell assays. The upregulation of PLS3 also led to enhanced phosphatidylinositol-3 kinase/protein kinase B signaling in PACA cells. These data suggest that PLS3 is a biomarker to estimate PACA progression and represents a molecular target for PACA therapy.

摘要

plastin-3 在癌细胞增殖和侵袭中发挥关键作用,但它在胰腺癌 (PACA) 中的预后价值仍未得到明确界定。在这项研究中,我们表明 PLS3 信使 RNA 在 PACA 组织中表达过度,与正常组织相比。我们积累了 207 例 PACA 标本进行免疫组织化学分析,并表明 PLS3 水平与 T 分类(p<.001)和病理学(p<.001)相关。此外,通过 Kaplan-Meier 生存分析评估,PLS3 高表达肿瘤的总生存率(p<.001)较差。通过多变量 Cox 回归分析发现,PLS3 是 PACA 的独立预后因素。此外,我们发现 PLS3 通过细胞计数试剂盒-8 测定、划痕愈合测定和 Transwell 测定增强肿瘤细胞的增殖和侵袭。PLS3 的上调也导致 PACA 细胞中磷脂酰肌醇-3 激酶/蛋白激酶 B 信号通路增强。这些数据表明,PLS3 是评估 PACA 进展的生物标志物,代表 PACA 治疗的分子靶点。

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