Department of Urology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, Hainan, China.
Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Tsinghua University, Beijing, China.
PLoS One. 2022 Jun 8;17(6):e0269595. doi: 10.1371/journal.pone.0269595. eCollection 2022.
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.
透明细胞肾细胞癌(ccRCC)是一种常见的肾癌,死亡率较高,因此发现新的治疗标志物对于改善患者的生存率至关重要。尿激酶型纤溶酶原激活物受体(PLAUR)在组织重塑和细胞外基质降解中发挥关键作用,这有助于肿瘤的侵袭和转移,是肿瘤恶性程度的主要特征。PLAUR 在 ccRCC 病理学中的作用尚未得到深入研究。在这项研究中,我们收集了来自 TCGA 数据库的 33 种肿瘤类型的每个患者的 mRNA 表达数据,并全面分析了肿瘤中 PLAUR 的表达与预后之间的相关性。然后,我们研究了 PLAUR 在 ccRCC 中的表达与 ccRCC 患者特定临床特征之间的关系。此外,我们分析了 PLAUR 在 ccRCC 中的功能和机制。我们的研究结果表明,PLAUR 在 ccRCC 中明显过表达,PLAUR 水平和 PLAUR 甲基化水平与不良预后显著相关。我们的研究结果还表明 PLAUR 参与了 ccRCC 的进展。PLAUR 的功能和机制分析结果表明,PLAUR 参与了 ccRCC 中的炎症和免疫相关途径;其他数据表明 PLAUR 的表达可能影响 ccRCC 中多种免疫细胞类型的浸润,并且 PLAUR 水平与免疫检查点的表达呈显著正相关。总之,我们的研究结果表明,高 PLAUR 表达可促进 ccRCC 向不良预后进展,因此 PLAUR 可能既可以作为预测巨噬细胞浸润和免疫微环境状态的潜在标志物,也可以作为 ccRCC 的重要免疫治疗靶点。