Identification and validation of SERPINE1 as a prognostic and immunological biomarker in pan-cancer and in ccRCC

Lingqin Li; Fan Li; Zhehao Xu; Liyang Li; Haiyi Hu; Yang Li; Shicheng Yu; Mingchao Wang; Lei Gao

doi:10.3389/fphar.2023.1213891

Identification and validation of SERPINE1 as a prognostic and immunological biomarker in pan-cancer and in ccRCC

Front Pharmacol. 2023 Aug 23:14:1213891. doi: 10.3389/fphar.2023.1213891. eCollection 2023.

Authors

Lingqin Li¹, Fan Li², Zhehao Xu², Liyang Li³, Haiyi Hu², Yang Li², Shicheng Yu², Mingchao Wang², Lei Gao²

Affiliations

¹ Department of Operating Room, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, HangZhou, China.
² Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
³ University of New South Wales, School of Medicine, Sydney, NSW, Australia.

Abstract

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.

Keywords: SERPINE1; cancer immunity; clear cell renal cell carcinoma; multi-omics; pan-cancer.