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一种与代谢重编程相关的基因特征与膀胱尿路上皮癌的预后和增殖相关。

A metabolic reprogramming-related gene signature correlates with prognosis and proliferation of BLCA.

作者信息

Wu Yaoxin, Luo Yi, Li Tinghao

机构信息

Health Management Center, First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong, Chongqing, 400016, People's Republic of China.

出版信息

Discov Oncol. 2024 Aug 8;15(1):338. doi: 10.1007/s12672-024-01219-2.

DOI:10.1007/s12672-024-01219-2
PMID:39115575
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11310377/
Abstract

Bladder cancer (BLCA) is one of the most frequent urothelium carcinoma, but with poor prognosis due to lack of reliable predictive biomarkers. Metabolic reprogramming involving in various nutrients, and is reported to be closely associated with malignant progression in BLCA. With the use of transcriptome sequencing data profiles of 349 patients from The Cancer Genome Atlas, we established a three-gene glycolysis-related signature to predict the prognosis of BLCA patients. Our signature constructed on the basis of AK3, GALK1 and NUP205 expression, detail features and interactions between these three genes were further explored. We established a nomogram by integrating clinical variables and the risk score. Glycolytic level and proliferation ability were detected to study the role and mechanisms of NUP205 on BLCA. The connections between three genes in our signature were independent. We found our signature gains more value for patients with highly malignant stage. The established nomogram also confirmed that the signature had a eligible clinically predict capacity. After inhibited NUP205 expression, we found the glycolysis level of BLCA cells decreased and proliferation ability suppressed, mainly through AMPK signaling pathway inactivation. Collectively, our study explored a three-gene glycolysis-related signature that predict the prognosis of patients with BLCA, and highlights NUP205 as a potential therapeutic target for inhibiting glycolytic processes and proliferation in BLCA cells.

摘要

膀胱癌(BLCA)是最常见的尿路上皮癌之一,但由于缺乏可靠的预测生物标志物,其预后较差。代谢重编程涉及多种营养物质,据报道与膀胱癌的恶性进展密切相关。利用来自癌症基因组图谱(The Cancer Genome Atlas)的349例患者的转录组测序数据,我们建立了一个三基因糖酵解相关特征来预测膀胱癌患者的预后。我们基于AK3、GALK1和NUP205的表达构建了特征,并进一步探索了这三个基因之间的详细特征和相互作用。我们通过整合临床变量和风险评分建立了一个列线图。检测糖酵解水平和增殖能力以研究NUP205在膀胱癌中的作用和机制。我们特征中的三个基因之间的联系是独立的。我们发现我们的特征对高恶性阶段的患者更有价值。所建立的列线图也证实了该特征具有合格的临床预测能力。抑制NUP205表达后,我们发现膀胱癌细胞的糖酵解水平降低,增殖能力受到抑制,主要是通过AMPK信号通路失活。总的来说,我们的研究探索了一种三基因糖酵解相关特征来预测膀胱癌患者的预后,并强调NUP205作为抑制膀胱癌细胞糖酵解过程和增殖的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fe2/11310377/f593c1a86b27/12672_2024_1219_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fe2/11310377/bc2ad2b7e52c/12672_2024_1219_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fe2/11310377/83f4b09e240e/12672_2024_1219_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fe2/11310377/f593c1a86b27/12672_2024_1219_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fe2/11310377/a6b6a238079c/12672_2024_1219_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fe2/11310377/adb624645080/12672_2024_1219_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fe2/11310377/cc645868e25f/12672_2024_1219_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fe2/11310377/07e59e7eb4eb/12672_2024_1219_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fe2/11310377/a9ca28d3d7e9/12672_2024_1219_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fe2/11310377/e56e15732edb/12672_2024_1219_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fe2/11310377/bc2ad2b7e52c/12672_2024_1219_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fe2/11310377/83f4b09e240e/12672_2024_1219_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fe2/11310377/f593c1a86b27/12672_2024_1219_Fig9_HTML.jpg

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本文引用的文献

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