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DAPK1 低表达与透明细胞肾细胞癌的不良预后和舒尼替尼耐药相关。

Low DAPK1 expression correlates with poor prognosis and sunitinib resistance in clear cell renal cell carcinoma.

机构信息

Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Aging (Albany NY). 2020 Nov 16;13(2):1842-1858. doi: 10.18632/aging.103638.

DOI:10.18632/aging.103638
PMID:33201837
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7880360/
Abstract

We investigated the prognostic significance of Death-Associated Protein Kinase 1 (DAPK1) and its role in sunitinib resistance in clear cell renal cell carcinoma (ccRCC). DAPK1 mRNA levels were significantly lower in tumor tissues than normal kidney tissues in TCGA-KIRC dataset (n=428). Both overall survival and disease-free survival were significantly shorter in ccRCC patients with low DAPK1 expression than those with high DAPK1 expression. Receiver operating characteristic curve analysis showed that low DAPK1 expression correlated with poor prognosis in ccRCC patients. Multivariate analysis confirmed that DAPK1 expression was an independent prognostic indicator in ccRCC. Gene set enrichment analysis showed that low DAPK1 expression correlates with upregulation of pathways related to metastasis, drug resistance, hypoxia and invasiveness in ccRCC patients. Sunitinib-resistant ccRCC cells show significantly lower DAPK1 mRNA and protein levels than sunitinib-sensitive ccRCC cells. DAPK1 overexpression enhances apoptosis in sunitinib-resistant ccRCC cells via the ATF6-dependent ER stress pathway. Xenograft tumors derived from DAPK1-overxpressing ccRCC cells were significantly smaller than the controls in nude mice. Our finding demonstrates that low DAPK1 expression is an independent prognostic indicator that correlates with ccRCC progression and sunitinib resistance.

摘要

我们研究了死亡相关蛋白激酶 1（DAPK1）在透明细胞肾细胞癌（ccRCC）中的预后意义及其在舒尼替尼耐药中的作用。TCGA-KIRC 数据集（n=428）中的肿瘤组织中 DAPK1mRNA 水平明显低于正常肾组织。DAPK1 低表达的 ccRCC 患者的总生存期和无病生存期均明显短于 DAPK1 高表达的患者。受试者工作特征曲线分析表明，DAPK1 低表达与 ccRCC 患者的不良预后相关。多变量分析证实，DAPK1 表达是 ccRCC 的独立预后指标。基因集富集分析表明，DAPK1 低表达与 ccRCC 患者中与转移、耐药、缺氧和侵袭性相关途径的上调相关。与舒尼替尼敏感的 ccRCC 细胞相比，舒尼替尼耐药的 ccRCC 细胞的 DAPK1mRNA 和蛋白水平明显降低。DAPK1 过表达通过 ATF6 依赖性内质网应激途径增强舒尼替尼耐药的 ccRCC 细胞的凋亡。在裸鼠中，源自 DAPK1 过表达 ccRCC 细胞的异种移植肿瘤明显小于对照。我们的研究结果表明，DAPK1 低表达是一个独立的预后指标，与 ccRCC 的进展和舒尼替尼耐药相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfad/7880360/cf510b7ca7f3/aging-13-103638-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfad/7880360/6ac7824bec45/aging-13-103638-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfad/7880360/95da413606fa/aging-13-103638-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfad/7880360/f6628a74cdc9/aging-13-103638-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfad/7880360/cf510b7ca7f3/aging-13-103638-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfad/7880360/6de316a1b866/aging-13-103638-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfad/7880360/bf3943ea175e/aging-13-103638-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfad/7880360/cf510b7ca7f3/aging-13-103638-g007.jpg

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Mol Oncol. 2019 Oct;13(10):2079-2097. doi: 10.1002/1878-0261.12545. Epub 2019 Aug 24.
2
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J Cancer. 2019 Feb 23;10(6):1398-1408. doi: 10.7150/jca.29571. eCollection 2019.
3
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单细胞二硫键程序性死亡调控模式指导肿瘤微环境的细胞间通讯，有助于肾透明细胞癌的进展和免疫治疗。
Front Immunol. 2024 Jan 16;15:1288240. doi: 10.3389/fimmu.2024.1288240. eCollection 2024.
4
Crosstalk between endoplasmic reticulum stress and multidrug-resistant cancers: hope or frustration.内质网应激与多药耐药性癌症之间的相互作用：希望还是挫折。
Front Pharmacol. 2023 Sep 18;14:1273987. doi: 10.3389/fphar.2023.1273987. eCollection 2023.
5
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J Cancer. 2023 Jul 31;14(12):2386-2398. doi: 10.7150/jca.83424. eCollection 2023.
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8
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9
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10
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