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跨膜蛋白88抑制肝细胞癌进展并作为一种新的预后因素。

Transmembrane protein 88 suppresses hepatocellular carcinoma progression and serves as a novel prognostic factor.

作者信息

Cai Lin, Du Yu, Song Kai, Peng Peng, Han Fei

机构信息

School of Food and Drug, Xuzhou Polytechnic College of Bioengineering, Xuzhou, China.

Department of Traditional Chinese Medicine, Xuzhou Kuangshan Hospital, Xuzhou, China.

出版信息

Front Oncol. 2023 Apr 6;13:1148498. doi: 10.3389/fonc.2023.1148498. eCollection 2023.

DOI:10.3389/fonc.2023.1148498
PMID:37091140
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10118034/
Abstract

BACKGROUND

Transmembrane protein 88 (TMEM88) is known to be involved in the canonical Wnt signaling pathway and is implicated in several malignancies. However, the expression, function, and prognostic significance of TMEM88 in hepatocellular carcinoma (HCC) remain unclear.

METHODS

In this study, we analyzed mRNA levels of TMEM88 in HCC specimens from the TCGA dataset (n=374) to explore the correlation between TMEM88 and HCC. We also overexpressed TMEM88 in the Huh7 human HCC cell line to investigate its tumor-related role in HCC. Additionally, we conducted experiments using a mouse model to further validate the critical function of TMEM88 in modulating HCC growth.

RESULTS

Our results showed that TMEM88 is negatively correlated with the T stage, TNM stage, and pathological grade of HCC. Higher levels of TMEM88 can help predict better overall survival of HCC in both univariate and multivariate analyses. Similarly, higher TMEM88 is a novel prognostic factor for better disease-specific survival of HCC. Overexpression of TMEM88 in Huh7 cells led to a decreased cell proliferation capacity. Xenograft experiments in a mouse model showed that TMEM88 overexpression can remarkably suppress HCC progression.

CONCLUSIONS

Transmembrane protein 88 suppresses HCC growth both and , which can act as a potential prognostic factor with clinical application potential.

摘要

背景

已知跨膜蛋白88(TMEM88)参与经典Wnt信号通路,并与多种恶性肿瘤有关。然而,TMEM88在肝细胞癌(HCC)中的表达、功能及预后意义仍不清楚。

方法

在本研究中,我们分析了来自TCGA数据集(n = 374)的HCC标本中TMEM88的mRNA水平,以探讨TMEM88与HCC之间的相关性。我们还在Huh7人HCC细胞系中过表达TMEM88,以研究其在HCC中的肿瘤相关作用。此外,我们使用小鼠模型进行实验,以进一步验证TMEM88在调节HCC生长中的关键功能。

结果

我们的结果表明,TMEM88与HCC的T分期、TNM分期及病理分级呈负相关。在单变量和多变量分析中,较高水平的TMEM88有助于预测HCC患者更好的总生存期。同样,较高的TMEM88水平是HCC患者疾病特异性生存期更好的一个新的预后因素。在Huh7细胞中过表达TMEM88导致细胞增殖能力下降。小鼠模型中的异种移植实验表明,TMEM88过表达可显著抑制HCC进展。

结论

跨膜蛋白88在体内和体外均抑制HCC生长,可作为具有临床应用潜力的潜在预后因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fbf/10118034/efb81bd06135/fonc-13-1148498-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fbf/10118034/461debe0a736/fonc-13-1148498-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fbf/10118034/b0d6ee6cf51f/fonc-13-1148498-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fbf/10118034/cb7e34a13eba/fonc-13-1148498-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fbf/10118034/be5d542a63ce/fonc-13-1148498-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fbf/10118034/54722bf01e3c/fonc-13-1148498-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fbf/10118034/efb81bd06135/fonc-13-1148498-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fbf/10118034/461debe0a736/fonc-13-1148498-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fbf/10118034/b0d6ee6cf51f/fonc-13-1148498-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fbf/10118034/cb7e34a13eba/fonc-13-1148498-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fbf/10118034/be5d542a63ce/fonc-13-1148498-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fbf/10118034/54722bf01e3c/fonc-13-1148498-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fbf/10118034/efb81bd06135/fonc-13-1148498-g006.jpg

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Targeting TMEM88 as an Attractive Therapeutic Strategy in Malignant Tumors.将TMEM88作为恶性肿瘤中一种有吸引力的治疗策略。
Front Oncol. 2022 Jun 6;12:906372. doi: 10.3389/fonc.2022.906372. eCollection 2022.
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TMEM88 Modulates Lipid Synthesis and Metabolism Cytokine by Regulating Wnt/β-Catenin Signaling Pathway in Non-Alcoholic Fatty Liver Disease.
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Immunotherapies for hepatocellular carcinoma.肝细胞癌的免疫疗法
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TMEM88 exhibits an antiproliferative and anti-invasive effect in bladder cancer by downregulating Wnt/β-catenin signaling.TMEM88 通过下调 Wnt/β-catenin 信号通路抑制膀胱癌的增殖和侵袭。
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