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Abstract
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.
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1 National Central University, Department of Life Sciences, Taoyuan, Taiwan (GRID:grid.37589.30) (ISNI:0000 0004 0532 3167); Taoyuan Armed Forces General Hospital, Division of Colon and Rectal Surgery, Department of Surgery, Taoyuan, Taiwan (GRID:grid.413912.c) (ISNI:0000 0004 1808 2366); Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (GRID:grid.278244.f) (ISNI:0000 0004 0638 9360)
2 Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (GRID:grid.278244.f) (ISNI:0000 0004 0638 9360); Taoyuan Armed Forces General Hospital, Medical Laboratory, Taoyuan, Taiwan (GRID:grid.413912.c) (ISNI:0000 0004 1808 2366)
3 Taoyuan Armed Forces General Hospital, Department of Pathology and Laboratory Medicine, Taoyuan, Taiwan (GRID:grid.413912.c) (ISNI:0000 0004 1808 2366)
4 Taoyuan Armed Forces General Hospital, Department of Emergency, Taoyuan, Taiwan (GRID:grid.413912.c) (ISNI:0000 0004 1808 2366)
5 Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (GRID:grid.278244.f) (ISNI:0000 0004 0638 9360); Tri-Service General Hospital, Division of Colon and Rectal Surgery, Department of Surgery, Taipei, Taiwan (GRID:grid.278244.f) (ISNI:0000 0004 0638 9360)
6 National Health Research Institutes, Institute of Cellular and System Medicine, Miaoli, Taiwan (GRID:grid.59784.37) (ISNI:0000000406229172)
7 National Central University, Department of Life Sciences, Taoyuan, Taiwan (GRID:grid.37589.30) (ISNI:0000 0004 0532 3167)