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MCL-1在犬肝细胞癌中的过表达及其作为预后标志物的效能

Overexpression of MCL-1 in canine hepatocellular carcinoma and its efficacy as a prognostic marker.

作者信息

Baek Jehun, Cho Jaeho, Shin Hun-Kyeong, Kim Wan Hee

机构信息

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, 1 Gwanak-Ro, Gwanak-Gu, Seoul, 08826, Republic of Korea.

出版信息

BMC Vet Res. 2025 May 16;21(1):349. doi: 10.1186/s12917-025-04798-6.

DOI:10.1186/s12917-025-04798-6
PMID:40380182
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12082996/
Abstract

BACKGROUND

Myeloid cell leukemia-1 (MCL-1)-an anti-apoptotic protein of the B-cell lymphoma 2 family-is commonly overexpressed in human cancers, promoting tumorigenesis and chemoresistance. Upregulated MCL-1 in human hepatocellular carcinoma (HCC) has been demonstrated in numerous studies, and therapeutic agents targeting this protein have been assessed. However, its prognostic significance in canine HCC remains unclear. The objective of this study was to detect MCL-1 protein in canine normal liver tissue and compare its expression level with that in HCC tissue using western blotting. Immunohistochemistry (IHC) was used to quantify MCL-1 intensity levels in normal, non-neoplastic hepatic diseases, and HCC tissues, and the differences were assessed. Additionally, the relevance of MCL-1 immunostaining to various clinical and pathological parameters was evaluated.

RESULTS

MCL-1 expression was markedly elevated in HCC tissues relative to normal liver tissues (P = 0.029). Additionally, all 10 normal liver tissues exhibited low IHC expression, which significantly increased as the malignancy progressed (P < 0.001). In the HCC samples, high MCL-1 immunostaining was substantially correlated with metastatic status (P = 0.034) and tumor size (P = 0.046). Moreover, survival curve analysis revealed a significant relationship between upregulated MCL-1 and lower disease-free survival and overall survival rate (P = 0.006 and P = 0.031, respectively).

CONCLUSION

MCL-1 expression is increased in canine HCC, and its overexpression significantly correlates to worse clinical outcomes. Therefore, MCL-1 is considered to be a promising prognostic marker.

摘要

背景

髓样细胞白血病-1(MCL-1)——一种B细胞淋巴瘤2家族的抗凋亡蛋白——在人类癌症中通常过度表达,促进肿瘤发生和化疗耐药性。众多研究已证实人类肝细胞癌(HCC)中MCL-1上调,并且针对该蛋白的治疗药物已得到评估。然而,其在犬类HCC中的预后意义仍不清楚。本研究的目的是使用蛋白质免疫印迹法检测犬正常肝组织中的MCL-1蛋白,并将其表达水平与HCC组织中的进行比较。免疫组织化学(IHC)用于量化正常、非肿瘤性肝病和HCC组织中的MCL-1强度水平,并评估差异。此外,还评估了MCL-1免疫染色与各种临床和病理参数的相关性。

结果

与正常肝组织相比,HCC组织中MCL-1表达明显升高(P = 0.029)。此外,所有10个正常肝组织均表现出低IHC表达,随着恶性程度进展显著增加(P < 0.001)。在HCC样本中,高MCL-1免疫染色与转移状态(P = 0.034)和肿瘤大小(P = 0.046)显著相关。此外,生存曲线分析显示MCL-1上调与无病生存率和总生存率降低之间存在显著关系(分别为P = 0.006和P = 0.031)。

结论

犬类HCC中MCL-1表达增加,其过表达与更差的临床结果显著相关。因此,MCL-1被认为是一个有前景的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/12082996/0b5de2080ade/12917_2025_4798_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/12082996/811914ca3168/12917_2025_4798_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/12082996/adaeb4942f3d/12917_2025_4798_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/12082996/0b5de2080ade/12917_2025_4798_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/12082996/811914ca3168/12917_2025_4798_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/12082996/adaeb4942f3d/12917_2025_4798_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/12082996/0b5de2080ade/12917_2025_4798_Fig3_HTML.jpg

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本文引用的文献

1
Evaluation of MCL-1 as a prognostic factor in canine mammary gland tumors.评估 MCL-1 在犬乳腺肿瘤中的预后价值。
PLoS One. 2024 Jul 16;19(7):e0306398. doi: 10.1371/journal.pone.0306398. eCollection 2024.
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Simultaneous Inhibition of Mcl-1 and Bcl-2 Induces Synergistic Cell Death in Hepatocellular Carcinoma.同时抑制Mcl-1和Bcl-2可诱导肝癌细胞发生协同性细胞死亡。
Biomedicines. 2023 Jun 8;11(6):1666. doi: 10.3390/biomedicines11061666.
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The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism.PI3K/AKT/mTOR 信号通路在肝癌代谢中的作用。
Int J Mol Sci. 2023 Jan 31;24(3):2652. doi: 10.3390/ijms24032652.
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Hallmarks of Cancer: New Dimensions.癌症的特征:新视角。
Cancer Discov. 2022 Jan;12(1):31-46. doi: 10.1158/2159-8290.CD-21-1059.
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Myeloid cell leukemia 1 (MCL-1): Structural characteristics and application in cancer therapy.髓系细胞白血病 1(MCL-1):结构特征及其在癌症治疗中的应用。
Int J Biol Macromol. 2021 Sep 30;187:999-1018. doi: 10.1016/j.ijbiomac.2021.07.166. Epub 2021 Jul 30.
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Understanding MCL1: from cellular function and regulation to pharmacological inhibition.理解 MCL1:从细胞功能和调控到药理学抑制。
FEBS J. 2022 Oct;289(20):6209-6234. doi: 10.1111/febs.16136. Epub 2021 Aug 2.
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Factors associated with survival in dogs with a histopathological diagnosis of hepatocellular carcinoma: 94 cases (2007-2018).与经组织病理学诊断为肝细胞癌的犬存活相关的因素:94 例病例报告(2007-2018 年)。
Open Vet J. 2021 Jan-Mar;11(1):144-153. doi: 10.4314/ovj.v11i1.21. Epub 2021 Feb 23.
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Targeting MCL-1 in cancer: current status and perspectives.靶向 MCL-1 在癌症中的治疗:现状与展望。
J Hematol Oncol. 2021 Apr 21;14(1):67. doi: 10.1186/s13045-021-01079-1.
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