Comprehensive analysis of the importance of PLAUR in the progression and immune microenvironment of renal clear cell carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is a common type of kidney cancer with a high mortality rate, and the discovery of new therapeutic markers is essential to improve patient survival. The plasminogen activator urokinase receptor (PLAUR) plays key roles in tissue remodeling and extracellular matrix degradation, which contribute to invasion and metastasis, a major feature of tumor malignancy. The role of PLAUR in ccRCC pathology has not been deeply studied. In this study, we collected the mRNA expression data of 33 tumor types, each derived from human patients obtained from TCGA database, and comprehensively analyzed the correlation between the expression of PLAUR in tumors and prognosis. Then, we studied the relationship between PLAUR expression in ccRCC and specific clinical features of ccRCC patients. In addition, we analyzed the function and mechanism of PLAUR in ccRCC. Our results showed that PLAUR was significantly overexpressed in ccRCC and that both PLAUR levels and PLAUR methylation levels significantly correlated with poor prognosis. Our results also suggest that PLAUR is involved in the progression of ccRCC. The results of functional and mechanistic analysis of PLAUR showed that PLAUR is involved in inflammatory and immune-related pathways in ccRCC; other data showed that PLAUR expression may affect the infiltration of multiple immune cell types in ccRCC and that PLAUR levels were significantly and positively correlated with the expression of immune checkpoints. In conclusion, our findings suggest that high PLAUR expression can promote the progression of ccRCC to poor prognosis, and thus PLAUR may serve as both a potential marker for predicting macrophage infiltration and immune microenvironment status and as an important immunotherapy target for ccRCC.

Identification of prognostic models for glycosylation-related subtypes and tumor microenvironment infiltration characteristics in clear cell renal cell cancer

“…For instance, the predictive biomarker ST3GAL5 has been linked to CD8 + T-cell depletion in ccRCC [ 21 ]. A poor prognosis for ccRCC can result from high PLAUR expression [ 22 ]. LGALS1 can predict probable immunological checkpoints and the effectiveness of anti-PD1 treatment in ccRCC patients [ 23 ].…”

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

“…Currently, the role of PLAUR in ccRCC remains unelucidated. Preliminary studies have found that PLAUR is significantly higher in ccRCC tissues, and the increased expression of PLAUR is tightly implicated in the poor prognosis of patient ( Wang et al, 2022a ; Wang et al, 2022b ). In the field of medicine, the search for effective therapeutic targets has always been a primary focus of scientists in treating various diseases.…”

“…Furthermore, the researchers suggest that an elevated expression of PLAUR is tightly linked to a poor prognosis in ccRCC. This gene not only serves as a crucial potential indicator for predicting macrophage infiltration and the immune microenvironment status, but also emerges as a promising target for ccRCC immunotherapy ( Wang et al, 2022b ). Based on these findings, we postulate that PLAUR can effectively serve as both a diagnostic and prognostic biomarker for ccRCC.…”

Construction and validation of a novel prognostic model of neutrophil‑related genes signature of lung adenocarcinoma

“…Its ligand uPA catalyzes plasminogen to form plasminogen and produces a proteolytic cascade, which contributes to tissue remodeling and ECM decomposition, and creates favorable conditions for tumor invasion and metastasis 49 . One study reported that PLAUR was significantly overexpressed in renal clear cell carcinoma and the level of PLAUR and PLAUR methylation was significantly correlated with poor prognosis and participated in the progression of renal clear cell carcinoma 50 . Similarly, Zhang et al demonstrated that PLAUR can promote the growth and metastasis of gastric cancer and promote the loss of nesting apoptosis tolerance in gastric cancer cells by constructing the MKN45 gastric cancer mouse model and gastric cancer cell suspension anoikis model for 24 h 51 .…”