Division of Disease Proteomics, Institute for Protein Research, Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Oncol Rep. 2011 May;25(5):1217-26. doi: 10.3892/or.2011.1198. Epub 2011 Mar 1.
The utility of CEA and CA19-9 as colorectal carcinoma (CRC) markers is limited and development of additional reliable markers is under investigation. We previously showed that galectin-1 is overexpressed in CRC tissues. If such a protein leaks into the peripheral circulation, it might constitute a tumor marker candidate. Here, we test the hypothesis that the levels of circulating galectins could reflect the presence of CRC and/or its progression state. We constructed sandwich ELISAs for galectin-1/-2/-3/-4/-7 and determined their plasma concentrations in 105 CRC patients and 100 healthy volunteers (control). Matched pair samples of 56 patients pre- and post-surgery were also subjected to ELISA analysis. Circulating levels of galectin-1/-3/-4 in CRC patients were significantly higher compared to those in controls. Galectin-1 and galectin-4 levels significantly decreased after surgery (P<0.01), and the level of galectin-4 in most patients fell below the cut-off value. The levels of circulating galectin-4 significantly increased as the tumor stage progressed (P<0.001), whereas those for galectin-1 were relatively high from an early stage. Combined use of galectin-4 with CEA and/or CA19-9 markedly increased the proportion of CRC patients who were positive for tumor markers (from 33.3 to 59.0% for CEA and from 17.1 to 51.4% for CA19-9). Our data show that galectin-4 may be a tumor marker for use in patient follow-up, while galectin-1 could be used for tumor screening. In particular, galectin-4 can be useful as a complementary marker when combined with CEA/CA19-9 to improve CRC follow-up.
癌胚抗原(CEA)和糖类抗原 19-9(CA19-9)作为结直肠癌(CRC)标志物的效用有限,因此正在研究开发其他可靠的标志物。我们之前曾表明,半乳糖凝集素-1 在 CRC 组织中过表达。如果这种蛋白质漏入外周循环,它可能构成肿瘤标志物候选物。在这里,我们检验了这样一个假设,即循环半乳糖凝集素的水平可以反映 CRC 的存在及其进展状态。我们构建了用于半乳糖凝集素-1/-2/-3/-4/-7 的夹心 ELISA,并在 105 名 CRC 患者和 100 名健康志愿者(对照组)中测定了其血浆浓度。还对 56 名患者术前和术后的配对样本进行了 ELISA 分析。与对照组相比,CRC 患者的循环半乳糖凝集素-1/-3/-4 水平明显更高。手术后半乳糖凝集素-1 和半乳糖凝集素-4 的水平显著降低(P<0.01),并且大多数患者的半乳糖凝集素-4 水平降至临界值以下。随着肿瘤分期的进展,循环半乳糖凝集素-4 的水平显著增加(P<0.001),而半乳糖凝集素-1 的水平在早期就相对较高。半乳糖凝集素-4 与 CEA 和/或 CA19-9 联合使用显著增加了肿瘤标志物阳性的 CRC 患者比例(CEA 从 33.3%增加到 59.0%,CA19-9 从 17.1%增加到 51.4%)。我们的数据表明,半乳糖凝集素-4 可能是用于患者随访的肿瘤标志物,而半乳糖凝集素-1 可用于肿瘤筛查。特别是,当与 CEA/CA19-9 联合使用时,半乳糖凝集素-4 可作为一种补充标志物,有助于改善 CRC 的随访。