Platelets promote metastasis of intrahepatic cholangiocarcinoma through activation of TGF-β/Smad2 pathway

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-02-18 DOI:10.1016/j.bbadis.2025.167734

Guijuan Luo , Shuyang Zhu , Liujie He , Qiang Liu , Chao Xu , Qinghua Yao , Heping Hu , Qiang Wang , Shanshan Zou

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引用次数: 0

Abstract

Intrahepatic cholangiocarcinoma (ICC), an aggressive liver cancer, lacks simple and accurate clinical tests, which poses challenges to postoperative diagnosis and treatment. Recent studies have indicated that platelet levels might be relevant to the postoperative prognosis of ICC. However, their prognostic significance in ICC remains unclarified. This study included 218 ICC patients who underwent hepatic resection. Comprehensive analyses of patients' postoperative prognosis were conducted primarily focusing on their platelet levels associated with prognostic traits. To further investigate the underlying mechanism between platelet levels and patients' postoperative prognosis, we elucidated the association between platelets and tumor metastasis using HCCC-9810 and HUCC-T1 cells as well as mouse models. In the retrospective cohort study, elevated serum platelet levels (≥300 × 10⁹/L) or tumoral platelet levels (≥0.23) individually indicated an unfavorable postoperative prognosis in individuals with ICC. Multivariate analysis showed that tumoral platelet levels can be an independent prognostic factor, while the loss of prognostic superiority of serum platelet levels in the analysis may be attributed to the influence of confounding inclusion variables. Epithelial/mesenchymal transition (EMT) marker expression changes in HCCC-9810 and HUCC-T1 cells with platelet treatment were analyzed to understand how platelets contribute to ICC malignant recurring progression. The significant role of the TGF-β/Smad2 pathway in ICC metastasis was identified. In addition, aspirin was found to have the potential to reduce ICC metastasis by inhibiting platelet function. In conclusion, this study indicated that ICC patients with postoperative serum platelet levels ≥300 × 10⁹/L or tumoral platelet levels ≥0.23 have significantly higher risk of poor postoperative prognosis. This is due to platelet-derived TGFβ1 leading to EMT in ICC cells, thus promoting tumor metastasis.

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.