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TBC1D1在胰腺癌中的预后价值及其与肿瘤微环境的关系：一项基于单细胞测序的研究

Prognostic Value of TBC1D1 and Its Relationship With the Tumor Microenvironment in Pancreatic Cancer: A Study Based on Single-Cell Sequencing.

作者信息

Yang Linfeng, Yan Duan, Yu Jun, Deng Dawei, Ma Lin, Yu Ruixin, Wei Song, Yu Jiahui, Lan Chuan, Yi Pengsheng

机构信息

Affiliated Hospital of North Sichuan Medical College Nanchong China.

Institute of Hepato-Biliary-Pancreatic-Intestinal Disease Affiliated Hospital of North Sichuan Medical College Nanchong China.

出版信息

FASEB Bioadv. 2025 Jul 9;7(7):e70034. doi: 10.1096/fba.2025-00092. eCollection 2025 Jul.

DOI:10.1096/fba.2025-00092
PMID:40641846
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12239688/
Abstract

TBC1 Domain Family Member 1 (TBC1D1) plays a crucial role in various cancers. However, its specific function in pancreatic cancer (PC) remains poorly understood. In this study, we aimed to evaluate the prognostic value of TBC1D1 and its correlation with the tumor microenvironment (TME) in PC. A total of 168 patients with PC were included in this study. The expression of TBC1D1 in patients was detected by immunohistochemistry. Additionally, single-cell RNA sequencing (scRNA-seq) was used to reveal the expression distribution and proportion of TBC1D1 across different cell populations. The relationship between TBC1D1 expression levels and the TME was further explored based on high and low TBC1D1 expression groups. Multivariate analysis revealed that TBC1D1 positivity was an independent adverse prognostic factor for overall survival (OS;  = 0.026). Immunohistochemistry and single-cell RNA sequencing analyses revealed that TBC1D1 expression was positively correlated with fibroblast activation protein, programmed cell death protein 1, and programmed cell death ligand-1 positivity but negatively correlated with clusters of differentiation 8T cells positivity. Our findings revealed that TBC1D1 is an independent prognostic risk factor in patients with PC and may promote PC progression by modulating the TME.

摘要

TBC1结构域家族成员1（TBC1D1）在多种癌症中发挥着关键作用。然而，其在胰腺癌（PC）中的具体功能仍知之甚少。在本研究中，我们旨在评估TBC1D1在PC中的预后价值及其与肿瘤微环境（TME）的相关性。本研究共纳入168例PC患者。通过免疫组织化学检测患者中TBC1D1的表达。此外，使用单细胞RNA测序（scRNA-seq）来揭示TBC1D1在不同细胞群体中的表达分布和比例。基于TBC1D1表达的高低分组，进一步探讨TBC1D1表达水平与TME之间的关系。多变量分析显示，TBC1D1阳性是总生存期（OS；P = 0.026）的独立不良预后因素。免疫组织化学和单细胞RNA测序分析显示，TBC1D1表达与成纤维细胞活化蛋白、程序性细胞死亡蛋白1和程序性细胞死亡配体1阳性呈正相关，但与分化簇8 T细胞阳性呈负相关。我们的研究结果表明，TBC1D1是PC患者的独立预后危险因素，可能通过调节TME促进PC进展。

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Int J Med Sci. 2024 Oct 7;21(13):2603-2612. doi: 10.7150/ijms.99744. eCollection 2024.
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TBC1 domain-containing proteins are frequently involved in triple-negative breast cancers in connection with the induction of a glycolytic phenotype.TBC1 结构域蛋白常与诱导糖酵解表型有关，与三阴性乳腺癌相关。
Cell Death Dis. 2024 Sep 4;15(9):647. doi: 10.1038/s41419-024-07037-2.
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Tumor-infiltrating T lymphocytes: A promising immunotherapeutic target for preventing immune escape in cholangiocarcinoma.
肿瘤浸润 T 淋巴细胞：预防胆管癌免疫逃逸的有前途的免疫治疗靶点。
Biomed Pharmacother. 2024 Aug;177:117080. doi: 10.1016/j.biopha.2024.117080. Epub 2024 Jul 6.
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The Importance of Stroma and Stromal SMA Expression in Pancreatic Ductal Adenocarcinoma.基质和基质 SMA 表达在胰腺导管腺癌中的重要性。
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TBC1D1 is an energy-responsive polarization regulator of macrophages via governing ROS production in obesity.TBC1D1 通过调节肥胖症中 ROS 的产生来调节巨噬细胞的能量响应性极化。
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