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FOXK2-FBXO32在乳腺癌肿瘤发生中的作用:对核糖体相关通路的见解

The role of FOXK2-FBXO32 in breast cancer tumorigenesis: Insights into ribosome-associated pathways.

作者信息

Liao Fuben, Zhu Jinjin, He Junju, Liu Zheming, Yao Yi, Song Qibin

机构信息

Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.

Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China.

出版信息

Thorac Cancer. 2025 Jan;16(1):e15482. doi: 10.1111/1759-7714.15482. Epub 2024 Nov 18.

DOI:10.1111/1759-7714.15482
PMID:39552461
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11729401/
Abstract

OBJECTIVE

To search for a new biomarker that can predict the efficacy and prognosis of tumor immunotherapy.

METHOD

FOXK2 genes were analyzed using single-cell sequencing in pan-cancer bulk RNA-seq from the TCGA database. We used algorithms to predict their immune infiltration. Functional enrichment and ChIP-seq identified potential downstream gene, FBXO32. FBXO32's role in cancer immune response was explored through analysis.

RESULTS

Significant up-regulation of FOXK2 was observed in prostate adenocarcinoma (PRAD), uterine corpus endometrial carcinoma (UCEC), bladder urothelial carcinoma (BLCA), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and stomach adenocarcinoma (STAD), while no such increase was found in lung cancer (lung adenocarcinoma [LUAD], lung squamous cell carcinoma [LUSC]) or thyroid carcinoma (THCA) tumor and adjacent tissues. FOXK2 expression correlated with patient prognosis, with lower expression associated with better immune response and survival and higher expression of its downstream gene FBXO32 linked to worse overall survival (OS) and immune infiltration. FOXK2 has the potential to be used as a prognostic indicator and target for treatment in individuals with cancer.

CONCLUSION

Our research provides insights into the significance of FOXK2 in cancer and indicates its potential as both a prognostic indicator and target for treatment. The ribosome-associated pathways involving FOXK2 and FBXO32 could be pivotal in the advancement of tumors, offering possible avenues for targeted and individualized immunotherapy approaches. Additional research is required to completely understand the mechanisms that are responsible for the participation of FOXK2 and its subsequent gene FBXO32 in cancer, as well as to explore the possible advantages of focusing on FOXK2 for cancer treatment.

摘要

目的

寻找一种能够预测肿瘤免疫治疗疗效和预后的新型生物标志物。

方法

利用TCGA数据库中泛癌批量RNA测序的单细胞测序分析FOXK2基因。我们使用算法预测其免疫浸润情况。功能富集和ChIP-seq鉴定出潜在的下游基因FBXO32。通过分析探索FBXO32在癌症免疫反应中的作用。

结果

在前列腺腺癌(PRAD)、子宫内膜癌(UCEC)、膀胱尿路上皮癌(BLCA)、结直肠癌(CRC)、胰腺导管腺癌(PDAC)和胃腺癌(STAD)中观察到FOXK2显著上调,而在肺癌(肺腺癌[LUAD]、肺鳞状细胞癌[LUSC])或甲状腺癌(THCA)的肿瘤及癌旁组织中未发现这种增加。FOXK2表达与患者预后相关,较低表达与更好的免疫反应和生存相关,其下游基因FBXO32的较高表达与较差的总生存期(OS)和免疫浸润相关。FOXK2有潜力作为癌症患者的预后指标和治疗靶点。

结论

我们的研究揭示了FOXK2在癌症中的重要性,并表明其作为预后指标和治疗靶点的潜力。涉及FOXK2和FBXO32的核糖体相关途径可能在肿瘤进展中起关键作用,为靶向和个体化免疫治疗方法提供了可能的途径。需要进一步研究以全面了解FOXK2及其后续基因FBXO32参与癌症的机制,以及探索专注于FOXK2进行癌症治疗的潜在优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/daf0801287e9/TCA-16-e15482-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/219b21b4405b/TCA-16-e15482-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/294576284c21/TCA-16-e15482-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/f8898778ac6b/TCA-16-e15482-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/f2c863546683/TCA-16-e15482-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/6b97de8ce245/TCA-16-e15482-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/d0cb98504e71/TCA-16-e15482-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/daf0801287e9/TCA-16-e15482-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/219b21b4405b/TCA-16-e15482-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/294576284c21/TCA-16-e15482-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/f8898778ac6b/TCA-16-e15482-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/f2c863546683/TCA-16-e15482-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/6b97de8ce245/TCA-16-e15482-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/d0cb98504e71/TCA-16-e15482-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/11729401/daf0801287e9/TCA-16-e15482-g008.jpg

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本文引用的文献

1
FBXO32 Stimulates Protein Synthesis to Drive Pancreatic Cancer Progression and Metastasis.FBXO32 通过刺激蛋白质合成促进胰腺癌的进展和转移。
Cancer Res. 2024 Aug 15;84(16):2607-2625. doi: 10.1158/0008-5472.CAN-23-3638.
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FBXO32-mediated degradation of PTEN promotes lung adenocarcinoma progression.FBXO32 介导的 PTEN 降解促进肺腺癌进展。
Cell Death Dis. 2024 Apr 20;15(4):282. doi: 10.1038/s41419-024-06635-4.
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FOXK2 transcriptionally activating VEGFA induces apatinib resistance in anaplastic thyroid cancer through VEGFA/VEGFR1 pathway.
FOXK2 通过转录激活 VEGFA 诱导甲状腺未分化癌对阿帕替尼产生耐药性,通过 VEGFA/VEGFR1 通路。
Oncogene. 2021 Oct;40(42):6115-6129. doi: 10.1038/s41388-021-01830-5. Epub 2021 Sep 6.
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FOXK2 downregulation suppresses EMT in hepatocellular carcinoma.FOXK2下调抑制肝细胞癌中的上皮-间质转化。
Open Med (Wars). 2020 Jul 20;15(1):702-708. doi: 10.1515/med-2020-0129. eCollection 2020.
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Prognostic Value of the FOXK Family Expression in Patients with Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy.新辅助放化疗后局部晚期直肠癌患者中FOXK家族表达的预后价值
Onco Targets Ther. 2020 Sep 16;13:9185-9201. doi: 10.2147/OTT.S255956. eCollection 2020.
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TIMER2.0 for analysis of tumor-infiltrating immune cells.TIMER2.0 用于分析肿瘤浸润免疫细胞。
Nucleic Acids Res. 2020 Jul 2;48(W1):W509-W514. doi: 10.1093/nar/gkaa407.
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A guide to cancer immunotherapy: from T cell basic science to clinical practice.癌症免疫疗法指南:从 T 细胞基础科学到临床实践。
Nat Rev Immunol. 2020 Nov;20(11):651-668. doi: 10.1038/s41577-020-0306-5. Epub 2020 May 20.
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A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors.单细胞和单细胞核 RNA-Seq 工具包,适用于新鲜和冷冻的人类肿瘤。
Nat Med. 2020 May;26(5):792-802. doi: 10.1038/s41591-020-0844-1. Epub 2020 May 11.
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A review of cancer immunotherapy toxicity.癌症免疫疗法毒性综述。
CA Cancer J Clin. 2020 Mar;70(2):86-104. doi: 10.3322/caac.21596. Epub 2020 Jan 16.
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