PLAUR as a Potential Biomarker Associated with Immune Infiltration in Bladder Urothelial Carcinoma

Abstract

Background Bladder urothelial carcinoma (BLCA) is one of the most lethal and aggressive malignancies of genitourinary system that affects human health. The urokinase plasminogen activator receptor (PLAUR) plays essential roles in tumorigenesis and immune modulation, and its aberrant expression is closely correlated with cancer progression. However, whether PLAUR has the potential to be one promising biomarker or immunotherapy target for BLCA is unknown. Methodology Various online databases were applied to assess the expression profile and prognostic value of PLAUR, as well as its correlation with immune infiltration in BLCA, including Oncomine, PrognoScan, TCGA, cBioPortal, TIMER, TISIDB, UALCAN, and MethSurv. The expression of PLAUR in BLCA was confirmed with ELISA assay for serum samples and immunohistochemistry for tissue samples. Results The results showed that the expression of PLAUR was elevated in BLCA, which was further confirmed by ELISA and immunohistochemistry. Patients with higher PLAUR level were predicted to have lower overall survival and disease specific survival rates, which were not impacted by the genetic alterations of PLAUR. In addition, the expression of PLAUR was positively associated with immune infiltration, and also the expression levels of gene markers of various immune cells. The negative correlation between PLAUR expression and PLAUR methylation level was observed, among which PLAUR expression was positively correlated with the abundance of 28 kinds of tumor-infiltrating lymphocytes, while PLAUR methylation level was negatively correlated with the abundance of 11 types of tumor-infiltrating lymphocytes. Moreover, the methylation level of PLAUR was closely correlated with patients’ clinicopathological features, and hypomethylation of PLAUR was associated with better outcomes of BLCA patients. Conclusion These findings suggested that PLAUR had the potential to serve as a valuable detection and prognostic biomarker or immunotherapeutic target for BLCA.

Comprehensive analysis of T cell exhaustion related signature for predicting prognosis and immunotherapy response in HNSCC

“…Oncostatin M (OSM) has been identified as significantly linked to tumor progression, potentially serving as a biomarker to predict OS in hepatocellular carcinoma [ 37 ]. Elevated levels of urokinase-type plasminogen activator receptor (PLAUR) was detected in bladder urothelial carcinoma, showing a correlation with the abundance of 28 types of tumor-infiltrating lymphocytes [ 38 ]. Increased expression of PLAUR indicated an unfavorable prognosis in glioma [ 39 ].…”

PLAUR facilitates the progression of clear cell renal cell carcinoma by activating the PI3K/AKT/mTOR signaling pathway

“…Accumulating studies have revealed the oncogenic significance of PLAUR. For example, recent studies have elucidated its pivotal role in the proliferation, invasion, and metastasis processes of esophageal cancer ( Xie et al, 2023 ), breast cancer ( Zhang et al, 2023 ), bladder urothelial carcinoma ( Liu et al, 2021 ), and prostate cancer ( Kimura et al, 2020 ). Zhang et al (2022) have demonstrated in vitro and in vivo that PLAUR promotes the malignant process of gastric cancer by affecting the cell cycle, apoptosis, and EMT.…”

Mitochondrial apoptosis-related gene polymorphisms are associated with responses to anthracycline-based chemotherapy in acute myeloid leukaemia

“…PLAUR , a membrane protein also known as urokinase-type plasminogen activator receptor (UPA-R, CD87), is mainly responsible for the expression of cellular plasmin, which promotes cell extravasation and tissue invasion. Studies have found that PLAUR is closely related to the occurrence and prognosis of a variety of malignant tumours ( 22 , 23 ). Furthermore, PLAUR gene polymorphism also affects the prognosis of tumours, with SNPs in the gene found to be associated with disease-free survival in breast cancer ( 24 ).…”