Background: Serpine Protease Inhibitorclade H1 (SERPINH1) is abnormally expressed in a variety of tumor tissues and is linked to the biological processes of tumorigenesis, migration, invasion, and metastasis. SERPINH1 expression and prognosis in malignant tumors, such as gastric, colorectal, and breast cancers, have previously been studied, but the gene has not yet been investigated in lung adenocarcinoma (LUAD) in terms of prognosis and the potential mechanisms of action.
Methods: SERPINH1 was identified as an independent prognostic factor for LUAD in The Cancer Genome Atlas (TCGA) cohort and Affiliated Hospital of Nantong University (NTU) cohort (the LUAD data set) by univariate and multivariate Cox regression analyses. Additionally, we performed immunohistochemical staining to analyze the expression of SERPINH1 in LUAD and normal lung tissue. Based on the TCGA database, we analyzed the correlation of this gene with the tumor mutation burden (TMB), tumor microenvironment, immune infiltration, immune checkpoints, and anti-tumor drugs using the R language-related R package.
Results: SERPINH1 was highly expressed in LUAD tissue. Kaplan-Meier survival curves in both the TCGA cohort and the NTU cohort showed that the SERPINH1 low-expression group had a higher survival rate than the high-expression group. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of the SERPINH1 co-expressed genes revealed that the gene was associated with the extracellular matrix and cell proliferation and migration. The analysis of SERPINH1 and the TMB revealed a superior survival advantage for patients with high TMB and high SERPINH1 expression, and worse survival for those with low TMB and high SERPINH1 expression. The analysis of the tumor microenvironment (TME) and immune infiltration revealed that the high and low expression of SERPINH1 was associated with different immune infiltration characteristics. The analysis of the immune checkpoints and anti-tumor drugs showed that immunotherapy and anti-neoplastic treatment were more efficacious in the high SERPINH1 expression group than the low SERPINH1 expression group.
Conclusions: Using LUAD tissues and clinical samples, we showed that SERPINH1 can be used as a prognostic biomarker for LUAD. Our findings provide a new approach and strategy for the clinical treatment of LUAD patients.
Keywords: Serpine Protease Inhibitorclade H1 (SERPINH1); immune infiltration; immunotherapy; lung adenocarcinoma; prognosis.
2022 Journal of Thoracic Disease. All rights reserved.