PLAUR作为与膀胱尿路上皮癌免疫浸润相关的潜在生物标志物。
PLAUR as a Potential Biomarker Associated with Immune Infiltration in Bladder Urothelial Carcinoma.
作者信息
Liu Mulin, Chen Siyi, Zhang Aihui, Zheng Qin, Fu Juan
机构信息
Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116011, People's Republic of China.
Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Dalian Medical University, Dalian, Liaoning Province, 116044, People's Republic of China.
出版信息
J Inflamm Res. 2021 Sep 15;14:4629-4641. doi: 10.2147/JIR.S326559. eCollection 2021.
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.
背景
膀胱尿路上皮癌（BLCA）是影响人类健康的最致命且侵袭性最强的泌尿生殖系统恶性肿瘤之一。尿激酶型纤溶酶原激活物受体（PLAUR）在肿瘤发生和免疫调节中发挥着重要作用，其异常表达与癌症进展密切相关。然而，PLAUR是否有可能成为BLCA的一种有前景的生物标志物或免疫治疗靶点尚不清楚。
方法
应用多个在线数据库评估PLAUR的表达谱、预后价值及其与BLCA免疫浸润的相关性，包括Oncomine、PrognoScan、TCGA、cBioPortal、TIMER、TISIDB、UALCAN和MethSurv。通过酶联免疫吸附测定法检测血清样本中PLAUR的表达，并用免疫组织化学法检测组织样本中PLAUR的表达，以证实其在BLCA中的表达情况。
结果
结果显示，BLCA中PLAUR的表达升高，这通过酶联免疫吸附测定法和免疫组织化学法得到进一步证实。PLAUR水平较高的患者预计总体生存率和疾病特异性生存率较低，且不受PLAUR基因改变的影响。此外，PLAUR的表达与免疫浸润呈正相关，也与各种免疫细胞的基因标志物表达水平呈正相关。观察到PLAUR表达与PLAUR甲基化水平呈负相关，其中PLAUR表达与28种肿瘤浸润淋巴细胞的丰度呈正相关，而PLAUR甲基化水平与11种肿瘤浸润淋巴细胞的丰度呈负相关。此外，PLAUR的甲基化水平与患者的临床病理特征密切相关，PLAUR低甲基化与BLCA患者的较好预后相关。
结论
这些发现表明，PLAUR有可能成为BLCA的一种有价值的检测和预后生物标志物或免疫治疗靶点。
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