背景：SERPINE1是一种丝氨酸蛋白酶抑制剂，参与调节纤溶酶原激活系统，最近被发现与癌症相关。然而，SERPINE1在全癌症中的临床意义和潜在机制仍不清楚。方法：在公共数据库中使用全癌症多组学数据，包括癌症基因组图谱（TCGA）和基因型-组织表达（GTEx），以及在线网络工具，分析了SERPINE1在不同癌症中的表达及其与预后、遗传变异、DNA启动子甲基化、生物过程、免疫调节因子表达水平、免疫细胞浸润肿瘤、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）、免疫治疗反应和药物敏感性的相关性。此外，还使用两个单细胞数据库，即肿瘤免疫单细胞中心2（TISCH2）和CancerSEA，探索了SERPINE1在单细胞水平上的表达和潜在作用。利用临床患者样本的定量逆转录PCR、使用基因表达组数据库The Gene Expression Omnibus（GEO）的独立队列进行验证，以及使用临床蛋白质组肿瘤分析协作组（CPTAC）数据库的蛋白质验证，进一步验证了SERPINE1在清液型肾癌（ccRCC）中的异常表达。结果：SERPINE1的表达在癌症中失调，并富集于内皮细胞和成纤维细胞。拷贝数扩增和低DNA启动子甲基化可能部分导致SERPINE1的高表达。SERPINE1的高表达与21种癌症的不良预后相关。基因集富集分析（GSEA）的结果表明SERPINE1参与免疫应答和肿瘤恶性度。SERPINE1的表达还与几个免疫调节因子和免疫细胞浸润相关，并可能发挥免疫抑制作用。此外，SERPINE1与TMB、MSI、免疫治疗反应以及多种药物的敏感性在癌症中相关。最后，通过对患者样本的定量逆转录PCR、六个独立的GEO队列以及CPTAC数据库的蛋白质数据验证了ccRCC中SERPINE1的高表达。结论：本研究的发现揭示了SERPINE1在各种类型的癌症中表现出异常表达，并与癌症免疫和肿瘤恶性度相关，为个体化癌症治疗提供了新的思路。版权所有©2023 Li, Li, Xu, Li, Hu, Li, Yu, Wang and Gao.

Background: SERPINE1, a serine protease inhibitor involved in the regulation of the plasminogen activation system, was recently identified as a cancer-related gene. However, its clinical significance and potential mechanisms in pan-cancer remain obscure. Methods: In pan-cancer multi-omics data from public datasets, including The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx), and online web tools were used to analyze the expression of SERPINE1 in different cancers and its correlation with prognosis, genetic alteration, DNA promoter methylation, biological processes, immunoregulator expression levels, immune cell infiltration into tumor, tumor mutation burden (TMB), microsatellite instability (MSI), immunotherapy response and drug sensitivity. Further, two single-cell databases, Tumor Immune Single-cell Hub 2 (TISCH2) and CancerSEA, were used to explore the expression and potential roles of SERPINE1 at a single-cell level. The aberrant expression of SERPINE1 was further verified in clear cell renal cell carcinoma (ccRCC) through qRT-PCR of clinical patient samples, validation in independent cohorts using The Gene Expression Omnibus (GEO) database, and proteomic validation using the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Results: The expression of SERPINE1 was dysregulated in cancers and enriched in endothelial cells and fibroblasts. Copy number amplification and low DNA promoter methylation could be partly responsible for high SERPINE1 expression. High SERPINE1 expression was associated with poor prognosis in 21 cancers. The results of gene set enrichment analysis (GSEA) indicated SERPINE1 involvement in the immune response and tumor malignancy. SERPINE1 expression was also associated with the expression of several immunoregulators and immune cell infiltration and could play an immunosuppression role. Besides, SERPINE1 was found to be related with TMB, MSI, immunotherapy response and sensitivity to several drugs in cancers. Finally, the high expression of SERPINE1 in ccRCC was verified using qRT-PCR performed on patient samples, six independent GEO cohorts, and proteomic data from the CPTAC database. Conclusion: The findings of the present study revealed that SERPINE1 exhibits aberrant expression in various types of cancers and is associated with cancer immunity and tumor malignancy, providing novel insights for individualized cancer treatment.Copyright © 2023 Li, Li, Xu, Li, Hu, Li, Yu, Wang and Gao.