Department of Clinical Oncology, Medical Faculty, Medical University of Plovdiv, Plovdiv, Bulgaria; University Hospital "Sveti Georgi" EAD, Plovdiv, Bulgaria.
Department of Clinical Laboratory, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv, Bulgaria; University Hospital "Sveti Georgi" EAD, Plovdiv, Bulgaria.
Biomol Biomed. 2023 Mar 16;23(2):287-297. doi: 10.17305/bjbms.2022.7857.
Alteration of urokinase plasminogen activator receptor (uPAR) in neoplasms is a prerequisite for invasiveness and metastatic ability. In the present study, we aimed to evaluate the relationship of pre-chemotherapy soluble uPAR (suPAR) with the odds for metastasis, lack of disease control, and its predictive ability for progression-free survival (PFS). Baseline plasma suPAR levels were measured by ELISA in 89 patients with various cancers prior to initiation of systemic treatment. Patients were followed prospectively until metastatic progression or death. TCGA Pan-Cancer dataset was mined for available RNAseq expression data of the PLAUR gene in patients with breast, colon, and lung cancer, and therelevant genomic and clinical data were extracted for further analysis. Pre-chemotherapy suPAR levels were significantly associated with white blood cell counts and fibrinogen and were significantly elevated both in patients with metastatic disease and in patients with progression. Increasing suPAR was significantly associated with odds for progression in the prespecified multivariate analysis (odds ratio 2.47, 95% confidence interval 1.3 - 5.11). In univariate Cox regression, suPAR was predictive of shortened progression-free survival (PFS) (hazard ratio 1.065, 95% confidence interval 1.002 - 1.13; p = 0.041). There was a trend towards shortened PFS in patients with higher baseline suPAR levels (cutoff 8.1 ng/mL). In the TCGA lung cancer cohort, PLAUR mRNA expression was significantly associated with shortened PFS in both univariate and multivariate analyses. High PLAUR gene expression conferred significant survival disadvantage only in patients with colon and lung cancer. SuPAR may bear predictive potential for adverse outcomes in cancer, but its utility as a biomarker seems to be more pronounced in cancers with associated inflammatory state.
尿激酶型纤溶酶原激活物受体(uPAR)在肿瘤中的改变是侵袭性和转移能力的前提。本研究旨在评估化疗前可溶性 uPAR (suPAR)与转移、缺乏疾病控制的几率以及其对无进展生存期(PFS)的预测能力之间的关系。在开始全身治疗前，通过 ELISA 测量了 89 例不同癌症患者的基线血浆 suPAR 水平。前瞻性随访患者，直至出现转移进展或死亡。TCGA 泛癌数据集挖掘了乳腺癌、结肠癌和肺癌患者 PLAUR 基因的可用 RNAseq 表达数据，并提取了相关的基因组和临床数据进行进一步分析。化疗前 suPAR 水平与白细胞计数和纤维蛋白原显著相关，在转移性疾病患者和进展患者中均显著升高。在预先指定的多变量分析中，suPAR 水平的升高与进展的几率显著相关(比值比 2.47，95%置信区间 1.3-5.11)。在单变量 Cox 回归中，suPAR 是预测无进展生存期(PFS)缩短的因素(风险比 1.065，95%置信区间 1.002-1.13；p = 0.041)。suPAR 基线水平较高的患者 PFS 缩短趋势(p = 0.053)。在 TCGA 肺癌队列中，PLAUR mRNA 表达在单变量和多变量分析中均与 PFS 缩短显著相关。高 PLAUR 基因表达仅在结肠癌和肺癌患者中导致显著的生存劣势。suPAR 可能具有预测癌症不良结局的潜力，但作为一种生物标志物，其在具有相关炎症状态的癌症中的效用似乎更为显著。
