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鉴定CENPW作为透明细胞肾细胞癌的预后生物标志物和潜在治疗靶点。

Identification of CENPW as a prognostic biomarker and potential therapeutic target for clear cell renal cell carcinoma.

作者信息

Xiao Haibing, Xu Qili, Gao Yu, Wu Weikang, Wang Baojun, Li Haolin, Fei Mintian

机构信息

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, People's Republic of China.

Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, Anhui, People's Republic of China.

出版信息

Discov Oncol. 2025 Jun 18;16(1):1138. doi: 10.1007/s12672-025-02859-8.

DOI:10.1007/s12672-025-02859-8
PMID:40531390
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12176707/
Abstract

Centromere protein W (CENP-W) is essential for chromosome segregation and mitotic assembly and has been recognized as a prognostic marker in several cancers. However, its significance in clear-cell renal cell carcinoma (ccRCC) remains underexplored. To investigate this, we analyzed transcriptomic data from the National Center for Biotechnology Information (NCBI) and The Cancer Genome Atlas (TCGA) to evaluate CENP-W expression and its associations with clinical outcomes, prognosis, and immune-related markers. Kaplan-Meier survival analysis indicated that elevated CENP-W levels are significantly associated with poorer overall survival in ccRCC patients. Further meta- and multivariate analyses confirmed CENP-W as an independent negative prognostic factor. Gene Set Enrichment Analysis (GSEA) revealed the involvement of CENP-W in immune-related pathways, notably PI3K-Akt and Wnt signaling. Pearson correlation analysis revealed strong associations between CENP-W expression and immune cell infiltration, cancer-associated fibroblasts (CAFs), CTLA4, and PDCD1. qRT-PCR assays confirmed elevated CENP-W levels in ccRCC samples. Additionally, GSEA and GO enrichment highlighted a relationship between CENP-W and lipid metabolism, with reduced CENP-W expression leading to a significant decrease in lipid droplet accumulation. This study identifies CENP-W as a potential biomarker and prognostic indicator in ccRCC, offering insights into personalized therapeutic strategies integrating tumor immunity to enhance the efficacy of immunotherapy.

摘要

着丝粒蛋白W（CENP-W）对于染色体分离和有丝分裂组装至关重要，并且在多种癌症中已被视为一种预后标志物。然而，其在透明细胞肾细胞癌（ccRCC）中的意义仍未得到充分探索。为了对此进行研究，我们分析了来自美国国立生物技术信息中心（NCBI）和癌症基因组图谱（TCGA）的转录组数据，以评估CENP-W的表达及其与临床结局、预后和免疫相关标志物的关联。Kaplan-Meier生存分析表明，CENP-W水平升高与ccRCC患者较差的总生存期显著相关。进一步的荟萃分析和多变量分析证实CENP-W是一个独立的负面预后因素。基因集富集分析（GSEA）揭示了CENP-W参与免疫相关途径，特别是PI3K-Akt和Wnt信号通路。Pearson相关性分析揭示了CENP-W表达与免疫细胞浸润、癌症相关成纤维细胞（CAF）、CTLA4和PDCD1之间的强关联。qRT-PCR检测证实了ccRCC样本中CENP-W水平升高。此外，GSEA和GO富集突出了CENP-W与脂质代谢之间的关系，CENP-W表达降低导致脂滴积累显著减少。本研究将CENP-W确定为ccRCC中的一种潜在生物标志物和预后指标，为整合肿瘤免疫以提高免疫治疗疗效的个性化治疗策略提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/c284fc5bd355/12672_2025_2859_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/303475e0631e/12672_2025_2859_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/aa15d8d646cf/12672_2025_2859_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/1e820296229d/12672_2025_2859_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/ad672a5135a9/12672_2025_2859_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/564935367135/12672_2025_2859_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/278afdf90216/12672_2025_2859_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/c284fc5bd355/12672_2025_2859_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/303475e0631e/12672_2025_2859_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/0842c1713999/12672_2025_2859_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/aa15d8d646cf/12672_2025_2859_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/1e820296229d/12672_2025_2859_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/ad672a5135a9/12672_2025_2859_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/564935367135/12672_2025_2859_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/278afdf90216/12672_2025_2859_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3321/12176707/c284fc5bd355/12672_2025_2859_Fig8_HTML.jpg

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本文引用的文献

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Int J Biol Sci. 2025 Jan 1;21(2):614-631. doi: 10.7150/ijbs.103032. eCollection 2025.
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Molecular mechanisms and clinical relevance of endothelial cell cross-talk in clear cell renal cell carcinoma.透明细胞肾细胞癌中内皮细胞串扰的分子机制及临床意义。
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MED15 is upregulated by HIF-2α and promotes proliferation and metastasis in clear cell renal cell carcinoma via activation of SREBP-dependent fatty acid synthesis.
MED15 被缺氧诱导因子-2α上调，并通过激活固醇调节元件结合蛋白（SREBP）依赖的脂肪酸合成促进透明细胞肾细胞癌的增殖和转移。
Cell Death Discov. 2024 Apr 22;10(1):188. doi: 10.1038/s41420-024-01944-1.
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The Role of MUC1 in Renal Cell Carcinoma.MUC1 在肾细胞癌中的作用。
Biomolecules. 2024 Mar 7;14(3):315. doi: 10.3390/biom14030315.
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Identify CTBP1-DT as an immunological biomarker that promotes lipid synthesis and apoptosis resistance in KIRC.鉴定 CTBP1-DT 为一种免疫生物标志物，可促进 KIRC 中的脂质合成和抗细胞凋亡。
Gene. 2024 Jul 1;914:148403. doi: 10.1016/j.gene.2024.148403. Epub 2024 Mar 21.
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Targeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma.靶向 MYC 通过上调透明细胞肾细胞癌中的 HILPDA 诱导脂滴积累。
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J Exp Clin Cancer Res. 2024 Jan 23;43(1):29. doi: 10.1186/s13046-023-02940-6.
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CENPW knockdown inhibits progression of bladder cancer through inducing cell cycle arrest and apoptosis.CENPW基因敲低通过诱导细胞周期停滞和凋亡来抑制膀胱癌的进展。
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