收稿日期: 2025-03-28
网络出版日期: 2025-07-18
基金资助
国家自然科学基金项目(82470691);上海市科学委员会基金项目(23JC1401306)
The role and prognostic value of matrix metalloproteinase 19 in colorectal cancer and its liver metastasis
Received date: 2025-03-28
Online published: 2025-07-18
目的 探究基质金属蛋白酶19（MMP-19）在结直肠癌（CRC）及肝转移（CRLM）中的功能及分子机制。 方法 整合并分析TCGA、GEO数据库中CRC及CRLM患者的转录组、单细胞数据与临床资料。通过RNA测序数据分析与MMP-19表达相关的生物学功能，并采用qRT-PCR、Western blot和免疫组织化学染色检测MMP-19在原发灶与肝转移灶中的表达差异。此外，通过体外功能实验验证MMP-19对结直肠癌细胞增殖、侵袭及迁移的作用。 结果 MMP-19在CRC组织中呈高表达，且与CRC、CRLM患者的不良预后显著相关。测序结果及功能富集分析表明MMP-19参与上皮间质转化、氨基酸蛋白转运、细胞增殖、细胞外基质组织构成及MAPK信号通路等生物学功能。单细胞分析显示在CRC原发灶及肝转移灶中，MMP-19在巨噬细胞和树突状细胞的表达高于正常组织。体外实验证实，MMP-19可增强结直肠癌细胞的增殖、侵袭及迁移能力。 结论 MMP-19可能通过诱导上皮间质转化及重塑免疫微环境，促进CRC的发生发展及增加术后复发及肝转移风险，有望成为CRC、CRLM诊断和治疗的新靶点。
何泽平 , 徐军明 . 基质金属蛋白酶19在结直肠癌及其肝转移中的作用与预后价值[J]. 实用医学杂志, 2025 , 41(13) : 1987 -1996 . DOI: 10.3969/j.issn.1006-5725.2025.13.007
Objective To explore the function and molecular mechanisms of matrix metalloproteinase 19 （MMP-19） in colorectal cancer （CRC） and liver metastasis of CRC （CRLM）. Methods This study comprehensively analyzed transcriptomic data， single-cell data， and clinical information of CRC and CRLM patients retrieved from public databases， namely The Cancer Genome Atlas （TCGA） and Gene Expression Omnibus （GEO）. RNA sequencing analysis was carried out to identify biological functions associated with MMP-19 expression. The differential expression of MMP-19 between primary lesions and liver metastatic lesions was evaluated using quantitative real-time polymerase chain reaction （qRT-PCR）， Western blotting， and immunohistochemistry. In vitro functional assays were performed to validate the impact of MMP-19 on the proliferation， invasion， and migration of colorectal cancer cells. Results MMP-19 was highly expressed in CRC tissues and was significantly correlated with poor prognosis in both CRC and CRLM patients. Sequencing results and functional enrichment analysis demonstrated that MMP-19 is involved in epithelial-mesenchymal transition， amino acid and protein transport， cell proliferation， extracellular matrix organization， and the mitogen-activated protein kinase （MAPK） signaling pathway. Single-cell analysis revealed that the expression of MMP-19 in macrophages and dendritic cells was higher in both CRC primary tumors and liver metastases compared to normal tissues. In vitro experiments confirmed that MMP-19 enhances the proliferation， invasion， and migration capabilities of colorectal cancer cells. Conclusion MMP-19 has been shown to play a crucial role in promoting the development and progression of CRC. It increases the risk of postoperative recurrence and liver metastasis through inducing epithelial-mesenchymal transition and remodeling the immune microenvironment. Given these findings， MMP-19 emerges as a promising novel target for the diagnosis and treatment of both CRC and CRLM.
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