Urokinase plasminogen activator predicts poor prognosis in hepatocellular carcinoma
Urokinase plasminogen activator predicts poor prognosis in hepatocellular carcinoma
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尿激酶纤溶酶原激活剂预测肝细胞癌的不良预后
DOI：
10.21037/jgo-21-343
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发表时间：
2021-07-22
影响因子：
2.1
通讯作者：
Song, Ye
中科院分区：
文献类型：
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作者：
Niu, Fei-Yu;Jin, Chuan;Song, Ye
背景：肝细胞癌（HCC）是世界范围内最常见的恶性肿瘤之一，其预后一直很差。因此，确定HCC的诊断和预后生物标志物非常重要。尿激酶型纤溶酶原激活物（Urokinase plasminogen activator，uPA）是一种降解细胞外基质（extracellular matrix，ECM）的蛋白酶，在肝癌的侵袭和转移中起着关键作用。方法：应用美国癌症基因组图谱（TCGA）数据库对uPA在肝癌组织中的表达进行分析，以确定uPA在肝癌中的临床意义。通过定量逆转录聚合链反应（qRT-PCR）进一步验证133对原发性HCC样本中uPA的表达水平。采用Kaplan-Meier方法对HCC样本和TCGA数据库进行生存分析。结果如下：我们的研究结果表明uPA在HCC中过表达，并且与HCC肿瘤大小（P=0.015）、分化级别（P=0.028）和肿瘤无包膜（P=0.010）显著相关。uPA高表达患者预后差（P=0.026）。TCGA数据库分析也与我们的实验结果一致。结论：总之，我们的研究结果表明，uPA在HCC中过表达，并与HCC的恶性特征，包括肿瘤的大小，分化程度和肿瘤包膜的缺乏。uPA高表达者生存期短。它是HCC的潜在预后生物标志物。
Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its prognosis remains dismal. Hence, it is important to identify the diagnostic and prognostic biomarkers for HCC. Urokinase plasminogen activator (uPA), an extracellular matrix (ECM)-degrading protease, plays a pivotal role in the invasion and metastasis of HCC. Methods: To confirm the clinical significance of uPA in HCC, we explored uPA expression in HCC in The Cancer Genome Atlas (TCGA) database. The expression level of uPA was further verified by quantitative reverse transcription polymerized chain reaction (qRT-PCR) in 133 pairs of primary HCC samples. A survival analysis was conducted with the Kaplan-Meier method in the HCC samples and TCGA database. Results: Our results showed that uPA was overexpressed in HCC and was significantly associated with HCC tumor size (P=0.015), differentiation grade (P=0.028), and absence of tumor encapsulation (P=0.010). Patients with high uPA expression levels had a poor outcome (P=0.026). TCGA database analysis was also consistent with our experimental results. Conclusions: In conclusion, our findings revealed that uPA was overexpressed in HCC and was related to HCC malignant features including tumor size, differentiation grade and absence of tumor encapsulation. High uPA expression had a shorter survival time. It is a potential prognostic biomarker of HCC.