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POSTN仅在癌症相关成纤维细胞中被激活，并导致胃癌患者预后不良。

POSTN is exclusively activated in cancer-associated fibroblasts and leads to unfavorable prognosis of patients with gastric cancer.

作者信息

To Ching Hei, Xie Fuda, Yu Peiyao, Wu Jialin, Lyu Yang, Chen Bonan, Feng Tiejun, Leung Hoi Wing, Kang Wei

机构信息

Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR 999077, P.R. China.

Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR 999077, P.R. China.

出版信息

Mol Clin Oncol. 2025 Jul 8;23(3):82. doi: 10.3892/mco.2025.2877. eCollection 2025 Sep.

DOI:10.3892/mco.2025.2877
PMID:40692747
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12278709/
Abstract

Drug resistance significantly impairs the prognosis of patients with gastric cancer (GC). As a key player in the acquisition of drug resistance, understanding the detailed evolution of the GC tumor microenvironment (TME) is crucial for improving therapeutic effectiveness. The clinical significance of markers related to cancer-associated fibroblast (CAF) proliferation and extracellular matrix remodeling were analyzed using public databases and immunohistochemistry staining on an in-house cohort of patients with GC. Combining this with single-cell RNA sequencing data revealed the expression patterns of all candidate markers, highlighting POSTN due to its pronounced upregulation in CAFs and its strong correlation with poor prognosis in patients with GC. Mechanistically, POSTN is directly regulated by the YAP1/TEAD1 co-transcription factor and is demonstrated to play significant roles in fibroblast proliferation and migration processes. The present study underscores POSTN as a promising marker for predicting GC prognosis and a powerful regulator that can augment the tumorigenic phenotypes of CAFs, providing a potential target to mitigate CAF-originated drug resistance.

摘要

耐药性显著损害胃癌（GC）患者的预后。作为获得耐药性的关键因素，了解GC肿瘤微环境（TME）的详细演变对于提高治疗效果至关重要。利用公共数据库和对一组GC患者的内部队列进行免疫组织化学染色，分析了与癌症相关成纤维细胞（CAF）增殖和细胞外基质重塑相关标志物的临床意义。将此与单细胞RNA测序数据相结合，揭示了所有候选标志物的表达模式，其中POSTN因其在CAF中显著上调且与GC患者预后不良密切相关而备受关注。从机制上讲，POSTN直接受YAP1/TEAD1共转录因子调控，并在成纤维细胞增殖和迁移过程中发挥重要作用。本研究强调POSTN是预测GC预后的一个有前景的标志物，也是增强CAF致瘤表型的有力调节因子，为减轻CAF源性耐药性提供了一个潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff8/12278709/13f1f0227db4/mco-23-03-02877-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff8/12278709/7e2788fbcefd/mco-23-03-02877-g00.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff8/12278709/271fd7fe2baf/mco-23-03-02877-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff8/12278709/5c77d96d5bc4/mco-23-03-02877-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff8/12278709/b6add22d90c9/mco-23-03-02877-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff8/12278709/2f265868dfd1/mco-23-03-02877-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff8/12278709/13f1f0227db4/mco-23-03-02877-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff8/12278709/7e2788fbcefd/mco-23-03-02877-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff8/12278709/40095084a198/mco-23-03-02877-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff8/12278709/271fd7fe2baf/mco-23-03-02877-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff8/12278709/5c77d96d5bc4/mco-23-03-02877-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff8/12278709/b6add22d90c9/mco-23-03-02877-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff8/12278709/2f265868dfd1/mco-23-03-02877-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ff8/12278709/13f1f0227db4/mco-23-03-02877-g06.jpg

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本文引用的文献

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Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.2022 年全球癌症统计数据：全球 185 个国家和地区 36 种癌症的发病率和死亡率全球估计数。
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