Department of Life Sciences, National Central University, Taoyuan, 320, Taiwan.
Division of Colon and Rectal Surgery, Department of Surgery, Taoyuan Armed Forces General Hospital, Taoyuan, 325, Taiwan.
Sci Rep. 2019 Mar 12;9(1):4228. doi: 10.1038/s41598-019-40862-6.
Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. We examined if tumor tissue and circulating protein levels of all vascular endothelial growth factors (VEGFs) and VEGF receptors (VEGFRs) were synchronous and different in Taiwan patients with metastatic CRC (mCRC) vs. non-mCRC. We analyzed samples from 109 patients enrolled from 2005-2017, 50 with stages I/II and 59 with stages III/IV CRC. We found that VEGF-A, -B, -C, -D, placental growth factor (PlGF), VEGFR-1, VEGFR-2, and VEGFR-3 were higher in tumor tissues than non-tumor tissues. Metastatic patients had higher levels of circulating VEGFs and soluble VEGFRs (sVEGFRs) than healthy subjects, as well as higher VEGF-A, -B, -C, -D, and PlGF proteins in both tumor tissue and serum than non-metastatic patients. Protein levels of VEGF and VEGFR were mainly associated with the patient's age, tumor site, tumor size, tumor stage, and lymph node metastasis. Patients exhibiting high levels of VEGF, VEGFR, and sVEGFR had a shorter overall survival and disease-free survival than those with low levels. We conclude that synchronous changes in VEGF and VEGFR levels in CRC tissue and serum VEGF can discriminate between metastatic and non-metastatic subjects and high levels are associated with poor survival in CRC.
结直肠癌（CRC）是全球癌症相关死亡的第三大主要原因。我们研究了台湾转移性 CRC（mCRC）患者与非转移性 CRC 患者的肿瘤组织和循环蛋白水平的所有血管内皮生长因子（VEGFs）和血管内皮生长因子受体（VEGFRs）是否同步且存在差异。我们分析了 2005 年至 2017 年间招募的 109 名患者的样本，其中 50 名患者为 I/II 期，59 名患者为 III/IV 期 CRC。我们发现，VEGF-A、-B、-C、-D、胎盘生长因子（PlGF）、VEGFR-1、VEGFR-2 和 VEGFR-3 在肿瘤组织中的水平高于非肿瘤组织。转移性患者的循环 VEGFs 和可溶性 VEGFRs（sVEGFRs）水平高于健康受试者，且肿瘤组织和血清中的 VEGF-A、-B、-C、-D 和 PlGF 蛋白水平均高于非转移性患者。VEGF 和 VEGFR 蛋白水平主要与患者的年龄、肿瘤部位、肿瘤大小、肿瘤分期和淋巴结转移有关。VEGF、VEGFR 和 sVEGFR 水平较高的患者的总生存期和无病生存期均短于水平较低的患者。我们得出结论，CRC 组织和血清 VEGF 中 VEGFs 和 VEGFR 水平的同步变化可区分转移性和非转移性患者，高水平与 CRC 患者的不良预后相关。
