• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

缺氧上调TPM4表达以增强上皮-间质转化，从而促进甲状腺乳头状癌的淋巴结转移。

Hypoxia upregulate TPM4 expression to strengthen epithelial-mesenchymal transition that promotes lymph node metastasis of papillary thyroid cancer.

作者信息

Li Zhufeng, Li Fuxin, Jiang Xunzhen, Li Yingxi, Jia Lanning, Wang Xiaoning, Liu Yuanchao, Jiang Ruoyu, Zhao Ke, Pu Guangmei, Tian Yao, Wang Yizeng, He Xianghui

机构信息

Department of General Surgery, Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin Medical University General Hospital, Tianjin General Surgery Institute, Tianjin, 300052, China.

Department of General Surgery, Tianjin Haihe Hospital, Tianjin, 300350, China.

出版信息

J Cancer. 2025 Jul 11;16(10):3216-3234. doi: 10.7150/jca.116524. eCollection 2025.

DOI:10.7150/jca.116524
PMID:40740237
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12305566/
Abstract

Papillary thyroid cancer (PTC) exhibits a high propensity for lymph node metastasis (LNM), significantly impacting postoperative recurrence and patient prognosis. The hypoxic microenvironment critically drives tumor progression by promoting PTC dedifferentiation. Through integrated bioinformatics analysis combining weighted gene co-expression network analysis and machine learning approaches on TCGA data, we identified TPM4 as a key hypoxia-responsive gene in PTC and validated its association with LNM using GEO datasets. Gene set enrichment analysis demonstrated that patients with high TPM4 expression in both TCGA and GEO databases showed significant enrichment in hypoxia and epithelial-mesenchymal transition (EMT) pathways. Single-cell pseudotime analysis revealed concurrent increases in hypoxia pathway enrichment, TPM4 expression, and EMT pathway activation during cell differentiation. Experimental validation using RT-qPCR and Western blot analyses confirmed that hypoxia-induced TPM4 upregulation activated EMT signaling. Functional assays demonstrated that TPM4 enhanced cellular invasion and migration capabilities. Our findings illuminate a novel mechanism whereby the hypoxic tumor microenvironment promotes lymph node metastasis in PTC through TPM4-mediated activation of EMT signaling, providing new insights into LNM of PTC.

摘要

甲状腺乳头状癌（PTC）具有较高的淋巴结转移（LNM）倾向，对术后复发和患者预后有显著影响。缺氧微环境通过促进PTC去分化，在肿瘤进展中起关键作用。通过对TCGA数据进行加权基因共表达网络分析和机器学习方法相结合的综合生物信息学分析，我们确定TPM4是PTC中关键的缺氧反应基因，并使用GEO数据集验证了其与LNM的关联。基因集富集分析表明，在TCGA和GEO数据库中TPM4高表达的患者在缺氧和上皮-间质转化（EMT）途径中显著富集。单细胞伪时间分析显示，在细胞分化过程中，缺氧途径富集、TPM4表达和EMT途径激活同时增加。使用RT-qPCR和蛋白质免疫印迹分析进行的实验验证证实，缺氧诱导的TPM4上调激活了EMT信号。功能实验表明，TPM4增强了细胞的侵袭和迁移能力。我们的研究结果揭示了一种新机制，即缺氧肿瘤微环境通过TPM4介导的EMT信号激活促进PTC中的淋巴结转移，为PTC的LNM提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/6f9bdac423df/jcav16p3216g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/b25f77a12f26/jcav16p3216g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/7b88489efdbe/jcav16p3216g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/0667f6e5858b/jcav16p3216g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/89f6e80c1f4c/jcav16p3216g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/a778d72a458d/jcav16p3216g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/16eeb9797ada/jcav16p3216g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/dabe3a6cb900/jcav16p3216g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/18980ece2279/jcav16p3216g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/20d751f6da41/jcav16p3216g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/6f9bdac423df/jcav16p3216g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/b25f77a12f26/jcav16p3216g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/7b88489efdbe/jcav16p3216g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/0667f6e5858b/jcav16p3216g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/89f6e80c1f4c/jcav16p3216g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/a778d72a458d/jcav16p3216g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/16eeb9797ada/jcav16p3216g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/dabe3a6cb900/jcav16p3216g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/18980ece2279/jcav16p3216g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/20d751f6da41/jcav16p3216g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f2a/12305566/6f9bdac423df/jcav16p3216g010.jpg

相似文献

1
Hypoxia upregulate TPM4 expression to strengthen epithelial-mesenchymal transition that promotes lymph node metastasis of papillary thyroid cancer.缺氧上调TPM4表达以增强上皮-间质转化，从而促进甲状腺乳头状癌的淋巴结转移。
J Cancer. 2025 Jul 11;16(10):3216-3234. doi: 10.7150/jca.116524. eCollection 2025.
2
Expression of WNT10A in papillary thyroid carcinoma and its effect on cell proliferation, invasion, and metastasis.WNT10A在甲状腺乳头状癌中的表达及其对细胞增殖、侵袭和转移的影响。
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2025 Mar 28;50(3):402-415. doi: 10.11817/j.issn.1672-7347.2025.240237.
3
ASAP1 Promotes Epithelial to Mesenchymal Transition by Activating the TGFβ Pathway in Papillary Thyroid Cancer.ASAP1通过激活甲状腺乳头状癌中的TGFβ信号通路促进上皮-间质转化
Cancer Med. 2025 Aug;14(15):e71075. doi: 10.1002/cam4.71075.
4
Single-cell perspective on the Monocyte-to-HDL cholesterol ratio as a metastasis biomarker in papillary thyroid cancer.单细胞视角下单核细胞与高密度脂蛋白胆固醇比值作为甲状腺乳头状癌转移生物标志物的研究
BMC Cancer. 2025 Jul 23;25(1):1203. doi: 10.1186/s12885-025-14373-9.
5
Hypoxia-induced MIR31HG expression promotes partial EMT and basal-like phenotype in pancreatic ductal adenocarcinoma based on data mining and experimental analyses.基于数据挖掘和实验分析，缺氧诱导的MIR31HG表达促进胰腺导管腺癌中的部分上皮-间质转化和基底样表型。
J Transl Med. 2025 Mar 10;23(1):305. doi: 10.1186/s12967-025-06292-x.
6
PLAGL2 as a prognostic biomarker and an EMT-promoting factor in PDAC.PLAGL2作为胰腺癌的一种预后生物标志物和上皮-间质转化促进因子。
Sci Rep. 2025 Jul 14;15(1):25425. doi: 10.1038/s41598-025-09591-x.
7
Expression profiling and bioinformatics analysis of serum exosomal circular RNAs in lymph node metastasis of papillary thyroid carcinoma.甲状腺乳头状癌淋巴结转移中血清外泌体环状RNA的表达谱分析及生物信息学分析
J Biomed Res. 2024 May 25;39(2):1-15. doi: 10.7555/JBR.37.20230304.
8
Circ_PSD3 Stimulates Cell Proliferation, Migration, Invasion and Epithelial to Mesenchymal Transition (EMT) in Papillary Thyroid Carcinoma via the Regulation of miR-145-5p/miR-338-3p/HMGB3 Axis.环状PSD3通过调控miR-145-5p/miR-338-3p/HMGB3轴刺激甲状腺乳头状癌细胞增殖、迁移、侵袭及上皮-间质转化（EMT）
J Biochem Mol Toxicol. 2025 Aug;39(8):e70402. doi: 10.1002/jbt.70402.
9
S100a4 promotes metastatic transformation in non-metastatic liver cancer cells through NMIIa binding: mechanistic insights.S100a4通过与NMIIa结合促进非转移性肝癌细胞的转移转化：机制洞察
BMC Cancer. 2025 Jul 4;25(1):1144. doi: 10.1186/s12885-025-14502-4.
10
BRAF mutation in papillary thyroid cancer and its value in tailoring initial treatment: a systematic review and meta-analysis.甲状腺乳头状癌中的BRAF突变及其在制定初始治疗方案中的价值：一项系统评价和荟萃分析。
Medicine (Baltimore). 2012 Sep;91(5):274-286. doi: 10.1097/MD.0b013e31826a9c71.

本文引用的文献

1
Integrating Bulk and Single-cell RNA-seq to Construct a Macrophage-related Prognostic Model for Prognostic Stratification in Triple-negative Breast Cancer.整合批量和单细胞RNA测序以构建三阴性乳腺癌预后分层的巨噬细胞相关预后模型
J Cancer. 2024 Sep 23;15(18):6002-6015. doi: 10.7150/jca.101042. eCollection 2024.
2
Identification of the tumor metastasis-related tumor subgroups overexpressed NENF in triple-negative breast cancer by single-cell transcriptomics.通过单细胞转录组学鉴定三阴性乳腺癌中过表达NENF的肿瘤转移相关肿瘤亚组。
Cancer Cell Int. 2024 Sep 18;24(1):319. doi: 10.1186/s12935-024-03505-z.
3
Integrated analysis of tumor microenvironment features to establish a diagnostic model for papillary thyroid cancer using bulk and single-cell RNA sequencing technology.
基于 bulk 和单细胞 RNA 测序技术的肿瘤微环境特征综合分析，建立甲状腺乳头状癌的诊断模型。
J Cancer Res Clin Oncol. 2023 Dec;149(18):16837-16850. doi: 10.1007/s00432-023-05420-8. Epub 2023 Sep 21.
4
TERT accelerates BRAF mutant-induced thyroid cancer dedifferentiation and progression by regulating ribosome biogenesis.TERT 通过调控核糖体生物发生促进 BRAF 突变型诱导的甲状腺癌去分化和进展。
Sci Adv. 2023 Sep;9(35):eadg7125. doi: 10.1126/sciadv.adg7125. Epub 2023 Aug 30.
5
m A-Dependent Modulation via IGF2BP3/MCM5/Notch Axis Promotes Partial EMT and LUAD Metastasis.m A 依赖性调节通过 IGF2BP3/MCM5/Notch 轴促进部分 EMT 和 LUAD 转移。
Adv Sci (Weinh). 2023 Jul;10(20):e2206744. doi: 10.1002/advs.202206744. Epub 2023 May 12.
6
Integrated pan-cancer analysis and experimental verification of the roles of tropomyosin 4 in gastric cancer.整合泛癌症分析和实验验证原肌球蛋白 4 在胃癌中的作用。
Front Immunol. 2023 Mar 13;14:1148056. doi: 10.3389/fimmu.2023.1148056. eCollection 2023.
7
Identification of novel immune subtypes and potential hub genes of patients with psoriasis.鉴定银屑病患者的新型免疫亚型和潜在的枢纽基因。
J Transl Med. 2023 Mar 8;21(1):182. doi: 10.1186/s12967-023-03923-z.
8
HIF-1α/YAP Signaling Rewrites Glucose/Iodine Metabolism Program to Promote Papillary Thyroid Cancer Progression.缺氧诱导因子 1α/Yes 相关蛋白信号通路重编程葡萄糖/碘代谢程序促进甲状腺乳头状癌进展。
Int J Biol Sci. 2023 Jan 1;19(1):225-241. doi: 10.7150/ijbs.75459. eCollection 2023.
9
Clinical Characterization and Prognostic Value of TPM4 and Its Correlation with Epithelial-Mesenchymal Transition in Glioma.TPM4在胶质瘤中的临床特征、预后价值及其与上皮-间质转化的相关性
Brain Sci. 2022 Aug 24;12(9):1120. doi: 10.3390/brainsci12091120.
10
Weighted gene Co-expression network analysis (WGCNA) reveals a set of hub genes related to chlorophyll metabolism process in chlorella (Chlorella vulgaris) response androstenedione.加权基因共表达网络分析（WGCNA）揭示了一组与小球藻（Chlorella vulgaris）响应雄烯二酮过程中的叶绿素代谢相关的枢纽基因。
Environ Pollut. 2022 Aug 1;306:119360. doi: 10.1016/j.envpol.2022.119360. Epub 2022 Apr 27.