Lomholt A F, Høyer-Hansen G, Nielsen H J, Christensen I J
Department of Surgical Gastroenterology, Copenhagen University Hospital Hvidovre, 30 Kettegaard Allé, DK-2650 Hvidovre, Denmark.
Br J Cancer. 2009 Sep 15;101(6):992-7. doi: 10.1038/sj.bjc.6605228. Epub 2009 Aug 11.
Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality in developed countries. It is known that early detection results in improved survival, and consequently there is a need for improved diagnostic tools in CRC. The plasma level of soluble urokinase plasminogen activator receptor (suPAR) was proposed as a marker in CRC patients. This study was undertaken to evaluate the individual molecular forms of suPAR as discriminators in a group of patients undergoing endoscopical examination following symptoms related to colorectal cancer.
In a case-control study comprising 308 patients undergoing endoscopical examination following CRC-related symptoms, 77 CRC patients with adenocarcinoma were age and gender matched to: 77 patients with adenomas; 77 with other non-malignant findings, and 77 with no findings. The different uPAR forms were measured in citrate plasma collected before endoscopical examination, using three different Time Resolved - Fluorescence Immuno Assays (TR-FIA's).
All soluble uPAR forms were found to be significantly higher in cancer patients than in patients presenting with other non-malignant findings; uPAR(I) P=0.0006, suPAR(I-III) P<0.0001 and suPAR(I-III)+(II-III) P<0.0001, whereas no significant difference was found when performing similar comparisons for patients presenting with adenomas. The odds ratio (OR) for the comparison of uPAR(I) in patients with CRC to subjects with other non-malignant findings was 3.44 (95% CI:1.86-6.37). CRC patients had a mean elevated level of 20.9% (95% CI:10.2-32.6) for suPAR(I-III) and 18.5% (95% CI:9.0-28.8) for suPAR(I-III)+(II-III) compared with subjects with non-malignant findings.
The findings confirm reports on increased uPAR expression in cancer patients and in particular elevated levels of suPAR in blood from CRC patients and indicate that suPAR levels in blood are increasing during carcinogenesis. Although none of the measured uPAR forms were cancer specific, our findings suggest that uPAR expression could be useful in the early detection of CRC when combined with other markers and clinical variables.
在发达国家，结直肠癌（CRC）是癌症相关发病和死亡的主要原因。众所周知，早期检测可提高生存率，因此需要改进CRC的诊断工具。可溶性尿激酶型纤溶酶原激活物受体（suPAR）的血浆水平被提议作为CRC患者的一个标志物。本研究旨在评估suPAR的各个分子形式，作为一组因结直肠癌相关症状接受内镜检查的患者的鉴别指标。
在一项病例对照研究中，308例因CRC相关症状接受内镜检查的患者，77例腺癌CRC患者按年龄和性别匹配：77例腺瘤患者；77例有其他非恶性病变者；77例无病变者。在内镜检查前采集的枸橼酸盐血浆中，使用三种不同的时间分辨荧光免疫分析法（TR-FIA）测量不同的uPAR形式。
发现所有可溶性uPAR形式在癌症患者中均显著高于有其他非恶性病变的患者；uPAR(I) P=0.0006，suPAR(I-III) P<0.0001，suPAR(I-III)+(II-III) P<0.0001，而对腺瘤患者进行类似比较时未发现显著差异。CRC患者与有其他非恶性病变的受试者相比，uPAR(I)的比值比（OR）为3.44（95%CI：1.86-6.37）。与有非恶性病变的受试者相比，CRC患者的suPAR(I-III)平均升高水平为20.9%（9%CI：10.2-32.6），suPAR(I-III)+(II-III)平均升高水平为18.5%（95%CI：9.0-28.8）。
这些发现证实了关于癌症患者uPAR表达增加的报道，特别是CRC患者血液中suPAR水平升高，并表明血液中suPAR水平在致癌过程中升高。虽然所测量的uPAR形式均不是癌症特异性的，但我们的发现表明，当与其他标志物和临床变量结合时，uPAR表达可能有助于CRC的早期检测。
