Department of Surgery, University of Heidelberg, Heidelberg 69120, Germany.
J Immunother. 2010 Feb-Mar;33(2):219-24. doi: 10.1097/CJI.0b013e3181bed29f.
Pancreatic adenocarcinoma as an aggressive tumor still lacks specific markers. Resection offers the only potential cure, and earlier diagnosis could benefit many patients. Here, we analyzed siC3b as a potential diagnostic marker. Soluble iC3b is generated in the fluid phase after binding of autoantibodies to tumor cells and subsequent inactivation of the complement cascade by interaction with complement regulatory proteins. Two hundred thirty-two plasma samples from patients with adjuvant treatment after resection, from healthy volunteers, and from vulnerable patients were collected prospectively and analyzed for siC3b. Every 3 months, the patients underwent imaging and the results from siC3b enzyme-linked immunosorbent assay were categorized according to radiologically defined recurrence within 4 months after blood withdrawal. Furthermore, the regulatory factors of the complement system were analyzed in tumor cells and in urine. The most important finding was that up to 4 months before radiologically defined recurrence, siC3b plasma level is increased with a sensitivity and specificity resulting in an area under the curve of 0.85, which could be further increased by combining it with CA19.9 (area under the curve=0.92). Complement regulatory proteins are highly expressed in pancreatic carcinoma cells and detectable in the patient's urine. In summary, screening for siC3b in patients with an increased risk for pancreatic ductal adenocarcinoma (patients with chronic pancreatitis, hereditary pancreatitis, after curative resection, and patients with a variety of familial cancer syndromes) allows for early detection with high sensitivity, as siC3b plasma levels are increased up to 4 months before radiologic evidence. Sensitivity could be further increased by combining this approach with CA19.9.
胰腺导管腺癌是一种侵袭性肿瘤，目前仍缺乏特异性标志物。手术切除是唯一可能治愈的方法，早期诊断可以使许多患者受益。在这里，我们分析了 siC3b 作为一种潜在的诊断标志物。可溶性 iC3b 是在自身抗体与肿瘤细胞结合后，在液相中产生的，随后通过与补体调节蛋白相互作用使补体级联失活。前瞻性收集了 232 例接受辅助治疗后、来自健康志愿者和易患患者的血浆样本，并分析了 siC3b。每 3 个月，对患者进行影像学检查，并根据采血后 4 个月内影像学定义的复发情况对 siC3b 酶联免疫吸附试验的结果进行分类。此外，还分析了肿瘤细胞和尿液中补体系统的调节因子。最重要的发现是，在影像学定义的复发前长达 4 个月，siC3b 血浆水平升高，其灵敏度和特异性导致曲线下面积为 0.85，如果与 CA19.9 结合使用，则可以进一步提高（曲线下面积为 0.92）。补体调节蛋白在胰腺癌细胞中高度表达，并可在患者尿液中检测到。总之，对胰腺导管腺癌高危患者（慢性胰腺炎、遗传性胰腺炎、根治性切除术后患者和多种家族性癌症综合征患者）进行 siC3b 筛查可实现早期检测，具有较高的灵敏度，因为 siC3b 血浆水平在影像学证据出现前 4 个月就会升高。通过将这种方法与 CA19.9 结合使用，可以进一步提高灵敏度。
