Abstract
Background: Serpin peptidase inhibitor clade H, member 1 (SERPINH1) is a gene encoding a member of the serpin superfamily of serine proteinase inhibitors. The upregulated of SERPINH1 was associated with poor prognosis in breast cancer, stomach adenocarcinoma, and esophageal carcinoma. However, the role of SERPINH1 in pan-cancer is largely unexplored. Methods: SERPINH1 expression and the correlation with prognosis in human pan-cancer were analyzed by the Cancer Genome Atlas and the Genotype-Tissue Expression dataset. Pearson correlation analysis was applied to evaluate the role of SERPINH1 expression in tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), DNA methyltransferase, and common immunoregulators. Spearman’s correlation test was used to analysis SERPINH1 expression in tumor immune infiltration and infiltrating immune cells via the Tumor Immune Evaluation Resource database. Furtherly, immunohistochemistry staining of SERPINH1 was acquired from the Human Protein Atlas database for validation. Results: SERPINH1 was abnormally expressed in fourteen cancers. The high expression of SERPINH1 significantly reduced the overall survival (OS), disease-specific survival, and progression free interval in eleven cancers. Moreover, SERPINH1 expression was correlated with MMR, MSI, TMB, and DNA methylation in multiple types of cancer. Also, SERPINH1 expression showed strong association with immunoregulators and immune checkpoint markers in testicular germ cell tumors, brain lower grade glioma (LGG), pheochromocytoma and paraganglioma. In addition, SERPINH1 expression was related to immune cell infiltration in multiple cancers, particularly in breast invasive carcinoma, LGG, and liver hepatocellular carcinoma. The result of immunohistochemistry verification shown that SERPINH1 staining was higher in tumor samples than in normal tissue in colon adenocarcinoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma and cervical squamous cell carcinoma, which was consistent with the result of OS. Conclusion: Overall, these results indicate that SERPINH1 may serve as an important prognostic biomarker and correlate with tumor immunity in human pan-cancer.
Highlights
Cancer is a major public health problem and the second leading cause of mortality around the world (Beheshtirouy et al, 2021)
The result of immunohistochemistry verification shown that SERPINH1 staining was higher in tumor samples than in normal tissue in colon adenocarcinoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma and cervical squamous cell carcinoma, which was consistent with the result of overall survival (OS)
Based on the TCGA database, we found that SERPINH1 expression is relatively higher in BRCA, CHOL, COAD, esophageal carcinoma (ESCA), GBM, HNSC, KIRP, LIHC, LUAD, LUSC, READ, stomach adenocarcinoma (STAD), and THCA, BLCA (p < 0.01), and lower grade glioma (LGG) than those in nomal tissues (Figure 1A)
Summary
Cancer is a major public health problem and the second leading cause of mortality around the world (Beheshtirouy et al, 2021). In the treatment of cancer, immune response, protein dysfunction, specific gene mutations, disorders of intracellular signal transduction pathways had been targeted in the past 2 decades (Yeger et al, 2021). Clade H, member 1 (SERPINH1) encodes a member of the serpin superfamily of serine proteinase inhibitors. SERPINH1 is localized to the endoplasmic reticulum and plays a role in collagen biosynthesis as a collagen-specific molecular chaperone. Abnormal expression of this gene may be a marker for cancer, and the nucleotide polymorphisms in this gene may be associated with preterm birth caused by preterm premature rupture of membranes. Serpin peptidase inhibitor clade H, member 1 (SERPINH1) is a gene encoding a member of the serpin superfamily of serine proteinase inhibitors. The role of SERPINH1 in pan-cancer is largely unexplored
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