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

PLoS One. 2022 Jun 8;17(6):e0269595. doi: 10.1371/journal.pone.0269595. eCollection 2022.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Renal Cell* / immunology
  • Carcinoma, Renal Cell* / pathology
  • Humans
  • Kidney Neoplasms* / immunology
  • Kidney Neoplasms* / pathology
  • Prognosis
  • Receptors, Urokinase Plasminogen Activator* / genetics
  • Tumor Microenvironment / genetics

Substances

  • Biomarkers, Tumor
  • PLAUR protein, human
  • Receptors, Urokinase Plasminogen Activator

Grants and funding

This work was supported by Hainan Provincial Natural Science Foundation of China (820RC784), Hunan Provincial Natural Science Foundation of China (2021JJ40427) and The School-level scientific research project of Jishou University (Jdlc2021). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.