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SERPINE1在胃癌中的泛癌分析:聚焦免疫治疗与预后

Pan-cancer analysis of SERPINE1 with a concentration on immune therapeutic and prognostic in gastric cancer.

作者信息

Ju Yuming, Wang Zeshen, Wang Qiancheng, Jin Shiyang, Sun Pengcheng, Wei Yuzhe, Zhu Guanyu, Wang Kuan

机构信息

Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China.

出版信息

J Cell Mol Med. 2024 Aug;28(15):e18579. doi: 10.1111/jcmm.18579.

Abstract

The serine protease inhibitor clade E member 1 (SERPINE1) is a key modulator of the plasminogen/plasminase system and has been demonstrated to promote tumor progression and metastasis in various tumours. However, although much literature has explored the cancer-promoting mechanism of SERPINE1, the pan-cancer analyses of its predictive value and immune response remain unexplored. The differential expression, and survival analysis of SERPINE1 expression in multiple cancers were analysed using The Cancer Genome Atlas and Genotype-Tissue Expression database. Kaplan-Meier (K-M) plotter and survival data analysis were used to analyze the prognostic value of SERPINE1 expression, including overall survival (OS), disease-specific survival, disease-free interval and progression-free interval and investigated the relationship of SERPINE1 expression with microsatellite instability. We further analysed the correlation between the expression of SERPINE1 and immune infiltration. The Kyoto Encyclopaedia of Genes and Genomes pathway was used for enrichment analysis, and the Gene Set Enrichment Analysis (GSEA) database was used to perform pathway analysis. Finally, in vitro experiments demonstrated that knockdown or overexpression of SERPINE1 could alter the proliferation and migration of gastric cancer (GC) cells. The results indicated that SERPINE1 expression levels different significantly between cancer and normal tissues, meanwhile, it was highly expressed in various cancers. By analysing online data, it has been observed that the gene SERPINE1 exhibits heightened expression levels across a variety of human cancers, significantly impacting patient survival rates. Notably, the presence of SERPINE1 was strongly associated with decrease OS and disease-free survival in individuals diagnosed with GC. Furthermore, an observed link indicates that higher levels of SERPINE expression are associated with increased infiltration of immune cells in GC. Finally, in vitro experiments showed that knockdown or overexpression of SERPINE1 inhibited the growth, and migration, of GC cells. SERPINE1expression potentially represents a novel prognostic biomarker due to its significant association with immune cell infiltration in GC. This study shows that SERPINE1 is an oncogene that participates in regulating the immune infiltration and affecting the prognosis of patients in multiple cancers, especially in GC. These findings underscore the importance of further investigating the role of SERPINE1 in cancer progression and offer a promising direction for the development of new therapeutic strategies.

摘要

丝氨酸蛋白酶抑制剂E家族成员1(SERPINE1)是纤溶酶原/纤溶酶系统的关键调节因子,已被证明可促进多种肿瘤的进展和转移。然而,尽管有大量文献探讨了SERPINE1的促癌机制,但其预测价值和免疫反应的泛癌分析仍未得到探索。利用癌症基因组图谱和基因型-组织表达数据库分析了SERPINE1在多种癌症中的差异表达及生存分析。使用Kaplan-Meier(K-M)绘图仪和生存数据分析SERPINE1表达的预后价值,包括总生存期(OS)、疾病特异性生存期、无病间期和无进展间期,并研究SERPINE1表达与微卫星不稳定性的关系。我们进一步分析了SERPINE1表达与免疫浸润之间的相关性。使用京都基因与基因组百科全书通路进行富集分析,并使用基因集富集分析(GSEA)数据库进行通路分析。最后,体外实验表明,敲低或过表达SERPINE1可改变胃癌(GC)细胞的增殖和迁移。结果表明,SERPINE1在癌组织和正常组织中的表达水平差异显著,同时在多种癌症中高表达。通过分析在线数据,观察到基因SERPINE1在多种人类癌症中表达水平升高,显著影响患者生存率。值得注意的是,SERPINE1的存在与GC患者的OS降低和无病生存期密切相关。此外,观察到的一种联系表明,SERPINE表达水平较高与GC中免疫细胞浸润增加有关。最后,体外实验表明,敲低或过表达SERPINE1可抑制GC细胞的生长和迁移。由于SERPINE1表达与GC中的免疫细胞浸润显著相关,其可能代表一种新的预后生物标志物。本研究表明,SERPINE1是一种癌基因,参与调节免疫浸润并影响多种癌症患者的预后,尤其是在GC中。这些发现强调了进一步研究SERPINE1在癌症进展中的作用的重要性,并为新治疗策略的开发提供了一个有前景的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03ef/11291546/308aab8a93fb/JCMM-28-e18579-g008.jpg

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