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AKIP1表达升高与子宫内膜癌的肿瘤侵袭、较短生存时间及化疗敏感性降低相关。

Elevated AKIP1 expression is associated with tumor invasion, shorter survival time and decreased chemosensitivity in endometrial carcinoma.

作者信息

Li Aili, Li Aijing, Gao Xiangpeng, Zhang Tongyan, Ma Zhiling, Xiao Yalin, Zhao Fei

机构信息

Department of Gynecology, Handan Central Hospital, Handan, Hebei 056001, P.R. China.

Department of Gynecology, Renqiu People's Hospital, Cangzhou, Hebei 062550, P.R. China.

出版信息

Oncol Lett. 2022 Jun 20;24(2):268. doi: 10.3892/ol.2022.13388. eCollection 2022 Aug.

DOI:10.3892/ol.2022.13388
PMID:35782897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9247666/
Abstract

A-kinase-interacting protein 1 (AKIP1), as a recently discovered oncoprotein, promotes cell malignant behaviors in gynecological malignancies. To the best of our knowledge, no study reports its clinical value in patients with endometrial carcinoma. The present study aimed to explore the association between AKIP1 expression and clinical features and survival in patients with endometrial carcinoma, and to assess the effect of AKIP1 knockdown on the regulation of chemosensitivity . The tumor and adjacent tissue specimens from 101 patients with endometrial carcinoma were retrieved for AKIP1 protein expression analysis using an immunohistochemistry (IHC) assay. Meanwhile, specimens from 54 patients with endometrial carcinoma were analyzed for AKIP1 mRNA expression using reverse transcription-quantitative PCR. Furthermore, an experiment was conducted in the Ishikawa cell line to determine the effect of AKIP1 modification on the chemosensitivity of cisplatin and paclitaxel. AKIP1 IHC score (P<0.001) and mRNA expression levels (P<0.001) were increased in tumor tissues compared with those in adjacent tissues. Moreover, increased AKIP1 IHC score was associated with lymphovascular invasion (P=0.007), advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.002) and shorter overall survival (OS) time (P=0.035) in the patients with endometrial carcinoma. Meanwhile, upregulated AKIP1 mRNA expression levels were associated with lymphovascular invasion (P=0.020) and advanced FIGO stage (P=0.027) in the patients with endometrial carcinoma. Multivariate Cox regression showed that tumor AKIP1 protein expression (high vs. low) independently predicted a shorter OS time (P=0.036). Silencing of AKIP1 decreased Ishikawa cell viability when treated with 5, 10, 20 and 40 µM cisplatin (all P<0.05) and decreased the half maximal inhibitory concentration value of cisplatin (P=0.003), whereas its effect on paclitaxel chemosensitivity was less obvious. Overall, elevated AKIP1 expression was associated with tumor invasion, shorter survival time and decreased chemosensitivity in endometrial carcinoma.

摘要

A激酶相互作用蛋白1(AKIP1)作为一种最近发现的癌蛋白,在妇科恶性肿瘤中促进细胞的恶性行为。据我们所知,尚无研究报道其在子宫内膜癌患者中的临床价值。本研究旨在探讨AKIP1表达与子宫内膜癌患者临床特征及生存之间的关联,并评估敲低AKIP1对化疗敏感性调控的影响。收集101例子宫内膜癌患者的肿瘤组织及癌旁组织标本,采用免疫组织化学(IHC)检测分析AKIP1蛋白表达。同时,采用逆转录定量PCR分析54例子宫内膜癌患者标本中AKIP1 mRNA表达。此外,在 Ishikawa细胞系中进行实验,以确定AKIP1修饰对顺铂和紫杉醇化疗敏感性的影响。与癌旁组织相比,肿瘤组织中AKIP1 IHC评分(P<0.001)及mRNA表达水平(P<0.001)升高。此外,子宫内膜癌患者中,AKIP1 IHC评分升高与淋巴管浸润(P=0.007)、国际妇产科联盟(FIGO)晚期分期(P=0.002)及总生存(OS)时间缩短(P=0.035)相关。同时,子宫内膜癌患者中,AKIP1 mRNA表达水平上调与淋巴管浸润(P=0.020)及FIGO晚期分期(P=0.027)相关。多因素Cox回归分析显示,肿瘤AKIP1蛋白表达(高表达 vs. 低表达)可独立预测较短的OS时间(P=0.036)。用5、10、20和40µM顺铂处理时,敲低AKIP1可降低Ishikawa细胞活力(均P<0.05),并降低顺铂的半数最大抑制浓度值(P=0.003),而其对紫杉醇化疗敏感性的影响不太明显。总体而言,子宫内膜癌中AKIP1表达升高与肿瘤侵袭、生存时间缩短及化疗敏感性降低相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/292e/9247666/b157d2268a6c/ol-24-02-13388-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/292e/9247666/27195adf88de/ol-24-02-13388-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/292e/9247666/af319c036cd0/ol-24-02-13388-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/292e/9247666/625e1573cbf4/ol-24-02-13388-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/292e/9247666/b157d2268a6c/ol-24-02-13388-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/292e/9247666/27195adf88de/ol-24-02-13388-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/292e/9247666/af319c036cd0/ol-24-02-13388-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/292e/9247666/625e1573cbf4/ol-24-02-13388-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/292e/9247666/b157d2268a6c/ol-24-02-13388-g03.jpg

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Transl Cancer Res. 2020 Feb;9(2):726-734. doi: 10.21037/tcr.2019.11.47.
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AKIP1 promotes glioblastoma viability, mobility and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways.AKIP1通过调节CXCL1和CXCL8介导的NF-κB和AKT信号通路,促进胶质母细胞瘤的生存能力、迁移能力和放化疗抗性。
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Nuclear factor-κB signaling inhibitors revert multidrug-resistance in breast cancer cells.
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Sirtuin2 correlates with lymph node metastasis, increased FIGO stage, worse overall survival, and reduced chemosensitivity to cisplatin and paclitaxel in endometrial cancer.Sirtuin2 与淋巴结转移、FIGO 分期升高、总生存期缩短以及对顺铂和紫杉醇化疗敏感性降低相关,在子宫内膜癌中。
Ir J Med Sci. 2022 Feb;191(1):147-154. doi: 10.1007/s11845-021-02516-3. Epub 2021 Feb 10.
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