A systematic pan-cancer analysis of PXDN as a potential target for clinical diagnosis and treatment

Abstract

Peroxidasin (PXDN), also known as vascular peroxidase-1, is a newly discovered heme-containing peroxidase; it is involved in the formation of extracellular mesenchyme, and it catalyzes various substrate oxidation reactions in humans. However, the role and specific mechanism of PXDN in tumor are unclear, and no systematic pan-cancer studies on PXDN have been reported to date. This study employed data from multiple databases, including The Cancer Genome Atlas and The Genotype-Tissue Expression, to conduct a specific pan-cancer analysis of the effects of PXDN expression on cancer prognosis. Further, we evaluated the association of PXDN expression with DNA methylation status, tumor mutation burden, and microsatellite instability. Additionally, for the first time, the relationship of PXDN with the tumor microenvironment and infiltration of fibroblasts and different immune cells within different tumors was explored, and the possible molecular mechanism of the effect was also discussed. Our results provide a comprehensive understanding of the carcinogenicity of PXDN in different tumors and suggest that PXDN may be a potential target for tumor immunotherapy, providing a new candidate that could improve cancer clinical diagnosis and treatment.

Periostin is associated with prognosis and immune cell infiltration in pancreatic adenocarcinoma based on integrated bioinformatics analysis

“…Interestingly, we identified peroxidasin (PXDN, also known as vascular peroxidase‐1), whose expression was positively correlated with POSTN (Figure 4B). A recent bioinformatics study highlighted the involvement of PXDN in the infiltration of fibroblasts and various immune cells, suggesting its potential as a promising target for tumor immunotherapy 18 . CAFs and the tumor immune microenvironment have been identified as key factors in promoting tumor progression 19 .…”

“…and various immune cells, suggesting its potential as a promising target for tumor immunotherapy. 18 CAFs and the tumor immune microenvironment have been identified as key factors in promoting tumor progression. 19 Therefore, we analyzed whether POSTN expression influences the tumor immune microenvironment.…”

Peroxidasin is associated with a mesenchymal-like transcriptional phenotype and promotes invasion in metastatic melanoma

“…In addition to metastatic melanoma, PXDN is thought to contribute to the progression of numerous other types of solid cancers. (31–35). However, the mechanisms underlying the role of PXDN in cancer are currently not well understood.…”

“…In addition to metastatic melanoma, PXDN is thought to contribute to the progression of numerous other types of solid cancers. (31)(32)(33)(34)(35).…”

Peroxidasin Inhibition by Phloroglucinol and Other Peroxidase Inhibitors

“…PXDN was shown to play an adverse role in various cardiovascular conditions including hypertensionassociated endothelial dysfunction [16][17][18], vascular remodelling and calcification [19], cardiac hypertrophy [18], atherosclerosis [20][21][22], aortic aneurysms [23], ischemic cardiac injury and fibrosis [24], as well as pulmonary arterial hypertension [25]. PXDN is upregulated in tissue fibrosis [2,26] and contributes to the progression of numerous types of cancer [27][28][29][30][31][32]. PXDN activity was shown to promote angiogenesis [33] and PXDN expression is associated with an increased invasive potential of cancer cells [29], possibly due to the remodelling of the tumour ECM to promote a permissive environment for cell invasion and metastasis.…”