Serum levels of vascular endothelial growth factor as a predictor for colorectal cancer prognosis and diagnosis

Medhat Assem

doi:10.66632/eei-2026-34

Authors

Medhat Assem Department of Civil Engineering, College of Engineering and Information Technology, Onaizah Colleges, Qassim, Saudi Arabia Author medhat.asem@oc.edu.sa

https://doi.org/10.66632/eei-2026-34

Keywords:

Rectal Carcinoma, VEGF, CEA, CA19-9

Although early detection is essential, radical surgery remains the main treatment for colorectal cancer, a major cause of cancer-related fatalities. The blood markers used in clinical practice for colorectal cancer (CA19-9) are carbohydrate antigen and carcinoemberyonic antigen (CEA). Both are only used for surveillance and as prognostic markers for disease-free survival because of their limited sensitivity and specificity. They are not used for screening or diagnosis. Therefore, there is an urgent need for a serum marker that facilitates early detection. Since angiogenesis is essential to the development and spread of cancers, targeting it has been shown to be an effective anti-tumor therapy. Vascular endothelial growth factor (VEGF), whose serum quantity has been connected to a variety of human malignancies, is one of the primary inducers of angiogenesis and may be used as a prognostic marker for solid tumors. Examining VEGF expression in patients with colorectal cancer (CRC) and comparing the findings to the patients' clinicopathologic features was the aim of this study. 68 patients and 10 healthy controls had their serum levels of CEA and CA19-9 compared to their VEGF levels. The results showed that higher serum levels of VEGF in CRC patients were significantly correlated with levels of CEA and CA19-9. In conclusion, determining VEGF serum levels can aid in the diagnosis of colorectal cancer (CRC) patients and open the door to VEGF inhibitor-based tailored treatment of CRC patients.

[1] M. E. de Castro et al., “Relationship between vascular density and microenvironment in medullary thyroid carcinoma,” Endocr. Relat. Cancer, vol. 33, no. 3, 2026, doi: https://doi.org/10.1530/ERC-25-0260.

[2] L. Yang et al., “Exosomal FGG promotes colorectal cancer liver metastases through inducing angiogenic pre-metastatic niche formation,” Arch. Biochem. Biophys., vol. 774, p. 110625, 2025, doi: https://doi.org/10.1016/j.abb.2025.110625.

[3] A. M. Kabel, A. M. Ashour, D. A. Ali, and H. H. Arab, “The immunomodulatory effects of topiramate on azoxymethane-induced colon carcinogenesis in rats: The role of the inflammatory cascade, vascular endothelial growth factor, AKT/mTOR/MAP kinase signaling and the apoptotic markers,” Int. Immunopharmacol., vol. 98, p. 107830, 2021, doi: https://doi.org/10.1016/j.intimp.2021.107830.

[4] N. Payervand et al., “Exosomal circ_0084043 derived from colorectal cancer-associated fibroblasts promotes in vitro endothelial cell angiogenesis by regulating the miR-140–3p/HIF-1α/VEGF signaling axis,” Heliyon, vol. 10, no. 11, p. e31584, 2024, doi: https://doi.org/10.1016/j.heliyon.2024.e31584.

[5] M. Frenz, F.-J. Kaup, and S. Neumann, “Serum vascular endothelial growth factor in dogs with haemangiosarcoma and haematoma,” Res. Vet. Sci., vol. 97, no. 2, pp. 257–262, 2014, doi: https://doi.org/10.1016/j.rvsc.2014.08.005.

[6] D. F. Elessawi, M. M. Alkady, and I. M. Ibrahim, “Diagnostic and prognostic value of serum IL-23 in colorectal cancer,” Arab J. Gastroenterol., vol. 20, no. 2, pp. 65–68, 2019, doi: https://doi.org/10.1016/j.ajg.2019.05.002.

[7] D. N. Florescu et al., “Correlation of the Pro-Inflammatory Cytokines IL-1β, IL-6, and TNF-α, Inflammatory Markers, and Tumor Markers with the Diagnosis and Prognosis of Colorectal Cancer,” Life, vol. 13, no. 12, 2023, doi: 10.3390/life13122261.

[8] K. D. Steffensen, M. Waldstrøm, U. Jeppesen, H. J. Knudsen, I. Brandslund, and A. Jakobsen, “Preoperative Serum Levels of Epidermal Growth Factor Receptor, HER2, and Vascular Endothelial Growth Factor in Malignant and Benign Ovarian Tumors,” Clin. Ovarian Cancer, vol. 1, no. 2, pp. 127–134, 2008, doi: https://doi.org/10.3816/COC.2008.014.

[9] C.-L. Chou et al., “KLK10 Upregulation Drives Aggressiveness and Radioresistance and Has a Negative Prognostic Impact on Rectal Cancer,” Lab. Investig., vol. 106, no. 6, p. 106128, 2026, doi: https://doi.org/10.1016/j.labinv.2026.106128.

[10] Y. Mo, S. Wu, Y. Liu, Y. Liang, Z. Cai, and L. Liang, “LRPPRC promotes the progression of colorectal cancer via HIF-1ꭤ/VEGF-meditated angiogenesis,” Pathol. - Res. Pract., vol. 275, p. 156223, 2025, doi: https://doi.org/10.1016/j.prp.2025.156223.

[11] Q. Han, Y. Zhu, F. Xing, and Y. Xia, “Current opinions on CEA in the diagnosis and prognosis of colorectal cancer,” Transl. Oncol., vol. 70, p. 102835, 2026, doi: https://doi.org/10.1016/j.tranon.2026.102835.

[12] H. Komatsu et al., “Serum Vascular Endothelial Growth Factor-A as a Prognostic Biomarker for Epithelial Ovarian Cancer,” Int. J. Gynecol. Cancer, vol. 27, no. 7, pp. 1325–1332, 2017, doi: https://doi.org/10.1097/IGC.0000000000001027.

[13] W. M. Sheikh et al., “Chapter 8 - Ovarian cancer: vascular endothelial growth factor signaling dysregulation, potential proteomic techniques, therapeutic strategies, and future perspectives,” in Proteomics: A Promising Approach for Cancer Research, S. Ali, S. Majid, M. U. Rehman, and Y. F. Jamous, Eds., Academic Press, 2026, pp. 211–226. doi: https://doi.org/10.1016/B978-0-443-23908-3.00020-4.

[14] Z. Yuan, Y. Chen, S. Liu, L. Shen, and X. Wang, “Evaluation of serum SNORA33 as a novel biomarker in colorectal cancer screening,” Biochem. Biophys. Res. Commun., vol. 791, p. 152911, 2025, doi: https://doi.org/10.1016/j.bbrc.2025.152911.

[15] S. Ganatra et al., “Diagnosis and Management of Cardiovascular Adverse Effects of Targeted Oncology Therapies: Bruton’s Tyrosine Kinase, Immune Checkpoint, and Vascular Endothelial Growth Factor Inhibitors: 2025 ACC Concise Clinical Guidance: A Report of the American College,” JACC, vol. 87, no. 5, pp. 654–682, 2026, doi: https://doi.org/10.1016/j.jacc.2025.10.018.

[16] M. İnanç et al., “Prognostic value of tumor growth factor levels during chemotherapy in patients with metastatic colorectal cancer,” Med. Oncol., vol. 29, no. 5, pp. 3119–3124, 2012, doi: 10.1007/s12032-012-0250-8.

[17] K. A. Kwon et al., “Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and C-reactive protein level in colorectal cancer,” BMC Cancer, vol. 10, 2010, doi: 10.1186/1471-2407-10-203.

[18] H. Akbulut et al., “Prognostic role of serum vascular endothelial growth factor, basic fibroblast growth factor and nitric oxide in patients with colorectal carcinoma,” Cytokine, vol. 20, no. 4, pp. 184–190, 2002, doi: 10.1006/cyto.2002.1993.

[19] A. Nogués et al., “Endoglin (CD105) and VEGF as potential angiogenic and dissemination markers for colorectal cancer,” World J. Surg. Oncol., vol. 18, no. 1, pp. 1–12, 2020, doi: 10.1186/s12957-020-01871-2.

[20] S. I. Ishigami et al., “Predictive value of vascular endothelial growth factor (VEGF) in metastasis and prognosis of human colorectal cancer,” Br. J. Cancer, vol. 78, no. 10, pp. 1379–1384, 1998, doi: 10.1038/bjc.1998.688.

[21] R. T. P. Poon et al., “Serum vascular endothelial growth factor predicts venous invasion in hepatocellular carcinoma: A prospective study,” Ann. Surg., vol. 233, no. 2, pp. 227–235, 2001, doi: 10.1097/00000658-200102000-00012.

[22] F. De Vita et al., “Elevated Perioperative Serum Vascular Endothelial Growth Factor Levels in Patients with Colon Carcinoma,” Cancer, vol. 100, no. 2, pp. 270–278, 2004, doi: 10.1002/cncr.11911.

[23] W. Jelski and B. Mroczko, “Biochemical markers of colorectal cancer – present and future,” Cancer Manag. Res., vol. 12, pp. 4789–4797, 2020, doi: 10.2147/CMAR.S253369.

[24] L. Y. Dirix et al., “Serum basic fibroblst growth factor and vascular endothelial growth factor and tumour growth kinetics in advanced colorectal cancer,” Ann. Oncol., vol. 7, no. 8, pp. 843–848, 1996, doi: 10.1093/oxfordjournals.annonc.a010764.

[25] A. Takeda et al., “Clinical significance of serum vascular endothelial growth factor in colorectal cancer patients: correlation with clinicopathological factors and tumor markers.,” Oncol Rep, vol. 7, no. 2, pp. 333–341, 2000, doi: 10.3892/or.7.2.333.

[26] J.-C. Lee, N.-H. Chow, S.-T. Wang, and S.-M. Huang, “Prognostic value of vascular endothelial growth factor expression in colorectal cancer patients,” Eur. J. Cancer, vol. 36, no. 6, pp. 748–753, 2000, doi: https://doi.org/10.1016/S0959-8049(00)00003-4.

[27] R. S. Saad, Y. L. Liu, G. Nathan, J. Celebrezze, D. Medich, and J. F. Silverman, “Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer,” Mod. Pathol., vol. 17, no. 2, pp. 197–203, 2004, doi: https://doi.org/10.1038/modpathol.3800034.

[28] R. Bendardaf, H. Lamlum, and S. Pyrhönen, “Prognostic and predictive molecular markers in colorectal carcinoma,” Anticancer Res., vol. 24, no. 4, pp. 2519–2530, 2004.

[29] E. Lieto et al., “Expression of Vascular Endothelial Growth Factor (VEGF) and Epidermal Growth Factor Receptor (EGFR) is an Independent Prognostic Indicator of Worse Outcome in Gastric Cancer Patients,” Ann. Surg. Oncol., vol. 15, no. 1, pp. 69–79, 2008, doi: 10.1245/s10434-007-9596-0.

[30] G. Wang, Y. Wang, X. Yang, Y. Zhang, Y. Lu, and Y. Li, “The expression and diagnostic value of serum levels of EphA2 and VEGF-A in patients with colorectal cancer,” Cancer Biomarkers, vol. 31, no. 4, pp. 399–408, 2021, doi: 10.3233/CBM-201745.

[31] I. Zlobec and A. Lugli, “Prognostic and predictive factors in colorectal cancer,” Postgrad. Med. J., vol. 84, no. 994, pp. 403–411, 2008, doi: 10.1136/jcp.2007.054858.

[32] R. T. P. Poon, J. W. Y. Ho, C. S. W. Tong, C. Lau, I. O. L. Ng, and S.-T. Fan, “Prognostic significance of serum vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma,” Br. J. Surg., vol. 91, no. 10, pp. 1354–1360, 2004, doi: 10.1002/bjs.4594.

[33] R. Broll et al., “Vascular endothelial growth factor (VEGF) - A valuable serum tumour marker in patients with colorectal cancer?,” Eur. J. Surg. Oncol., vol. 27, no. 1, pp. 37–42, 2001, doi: 10.1053/ejso.2000.1052.

[34] N. Ilhan, H. Gungor, H. F. Gul, and H. Eroksuz, “Expression of endoglin and vascular endothelial growth factor as prognostic markers in experimental colorectal cancer,” Anticancer Res., vol. 36, no. 8, pp. 3953–3959, 2016.

[35] J. E. Peterson et al., “VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients,” Angiogenesis, vol. 15, no. 2, pp. 265–273, 2012, doi: 10.1007/s10456-012-9259-z.

[36] S. Zhong, Z. Zhang, and S. Li, “Significance of vascular endothelial growth factor expression in colorectal cancer,” Zhonghua Nei Ke Za Zhi, vol. 40, no. 8, pp. 514–516, 2001.

[37] M. Asem, A. T. Abbas, M. Al-Hemaly, A. Shalaby, and M. Sami, “Vascular endothelial growth factor serum level as a diagnostic and prognostic marker for colorectal carcinoma,” Life Sci. J., vol. 10, no. 3, pp. 1975–1981, 2013