Loosen Sven H, Tacke Frank, Binnebosel Marcel, Leyh Catherine, Vucur Mihael, Heitkamp Florian, Schoening Wenzel, Ulmer Tom F, Alizai Patrick H, Trautwein Christian, Koch Alexander, Longerich Thomas, Roderburg Christoph, Neumann Ulf P, Luedde Tom
Department of Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany.
Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, 52074 Aachen, Germany.
Oncotarget. 2018 Jun 5;9(43):27027-27038. doi: 10.18632/oncotarget.25471.
In colorectal cancer (CRC), the liver is the most common site of metastasis. Surgical resection represents the standard therapy for patients with colorectal liver metastases (CRLM). However, 5-year survival rates after resection do not exceed 50%, and despite existing preoperative stratification algorithms it is still debated which patients benefit most from surgical treatment. The soluble urokinase plasminogen activator receptor (suPAR) has recently evolved as a promising biomarker for distinct clinical conditions. Here, we examined a potential role of suPAR as a biomarker in patients undergoing resection of CRLM.
Correlating with upregulated uPAR tissue expression in resected metastases, serum concentrations of suPAR were significantly elevated in CRLM patients compared to healthy controls. Importantly, patients with preoperative suPAR serum levels above the identified ideal cut-off value of 4.83 ng/ml showed a significantly reduced overall survival after resection of CRLM, both in right- and left-sided primary CRC. Moreover, multivariate Cox regression analysis revealed preoperative suPAR serum levels as a prognostic factor for mortality. Additionally, elevated preoperative suPAR but not creatinine levels were a predictor of acute kidney injury (AKI) after CRLM resection, correlating with a longer postoperative hospitalization.
SuPAR represents a promising novel biomarker in CRLM patients that might help to guide preoperative treatment decisions regarding patients' outcome and to identify patients particularly susceptible to AKI.
Expression levels of uPAR were analyzed in CRLM tissue using RT-PCR and immunohistochemistry. SuPAR serum levels were measured by ELISA in 104 CRC patients undergoing hepatic resection for CRLM and 50 healthy controls.
在结直肠癌（CRC）中，肝脏是最常见的转移部位。手术切除是结直肠癌肝转移（CRLM）患者的标准治疗方法。然而，切除术后的5年生存率不超过50%，尽管存在现有的术前分层算法，但对于哪些患者从手术治疗中获益最大仍存在争议。可溶性尿激酶型纤溶酶原激活物受体（suPAR）最近已成为一种有前景的生物标志物，用于不同的临床情况。在此，我们研究了suPAR作为生物标志物在接受CRLM切除术患者中的潜在作用。
与切除转移灶中上调的uPAR组织表达相关，CRLM患者的血清suPAR浓度与健康对照相比显著升高。重要的是，术前suPAR血清水平高于确定的理想临界值4.83 ng/ml的患者，无论原发CRC位于右侧还是左侧，CRLM切除术后的总生存期均显著降低。此外，多变量Cox回归分析显示术前suPAR血清水平是死亡率的预后因素。此外，术前suPAR升高而非肌酐水平是CRLM切除术后急性肾损伤（AKI）的预测指标，与术后住院时间延长相关。
SuPAR是CRLM患者中有前景的新型生物标志物，可能有助于指导关于患者预后的术前治疗决策，并识别特别易患AKI的患者。
使用RT-PCR和免疫组织化学分析CRLM组织中uPAR的表达水平。通过ELISA测定104例接受CRLM肝切除术的CRC患者和50例健康对照的血清suPAR水平。
