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DOI: 10.1055/s-0041-1724065
Profiles of Endoglin and Vascular Endothelial Growth Factor Based on Staging and Histological Grading of Colorectal Cancer and Their Relationship with Bevacizumab Therapy
Perfis da endoglina e do fator de crescimento endotelial vascular com base no estadiamento e na graduação histológica do câncer colorretal e sua relação com a terapia com bevacizumabe Funding The present study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.Abstract
Objective The present study evaluated the profile of endoglin (CD105) and vascular endothelial growth factor (VEGF) based on staging and histopathological grading of colorectal cancer as well as their relationship with bevacizumab therapy.
Methods A total of 88 cases of colorectal adenocarcinoma were included in the present study. The levels of VEGF and CD105 protein were evaluated with enzyme-linked immunosorbent assay (ELISA).
Results There was a significant difference in the level of CD105 (p = 0.002) between metastases and non-metastases subjects, showing that CD105 was higher in metastases subjects (4.59 ng/ml). There was no significant difference in the level of VEGF based on the presence of metastasis (p = 0.625). There was a significant difference in the levels of CD105 (p = 0.038) and VEGF (p = 0.010) between the subjects who received chemotherapy and those who did not. The CD105 level was higher in the subjects who received chemotherapy (4.43 ng/ml); conversely, the level of VEGF was lower in subjects who received chemotherapy (543.65 pg/ml). There was a statistically significant difference in the levels of CD105 (p = 0.003) and VEGF (p = 0.002) between subjects who received bevacizumab therapy and subjects who did not. The levels of CD105 were higher in subjects who received bevacizumab therapy (5.11 ng/ml); in contrast, the level of VEGF was higher in subjects who did not receive bevacizumab therapy (645.92 pg/ml). There was a significant positive correlation between CD105 and VEGF in subjects who did not receive bevacizumab (p < 0.01).
Conclusion The results of this study support a hypothesis of “escape mechanism” in the failure of anti-angiogenesis therapy (anti-VEGF).
Resumo
Objetivo Este estudo avaliou o perfil da endoglina (CD105) e do fator de crescimento endotelial vascular (FCEV) com base no estadiamento e graduação histopatológica do câncer colorretal, assim como sua relação com a terapia com bevacizumabe.
Métodos No total, 88 casos de adenocarcinoma colorretal foram incluídos no presente estudo. Os níveis das proteínas FCEV e CD105 foram avaliados com ensaio imunoenzimático (ELISA, na sigla em inglês).
Resultados Houve uma diferença significativa no nível de CD105 (p = 0,002) entre indivíduos com metástases e sem metástases, que indicou que o nível de CD105 é mais alto em indivíduos com metástases (4,59 ng/ml). Não houve diferença significativa no nível de FCEV com base na presença de metástases (p = 0,625). Houve diferença significativa nos níveis de CD105 (p = 0,038) e de FCEV (p = 0,010) entre os indivíduos que receberam quimioterapia e os que não receberam. Encontrou-se um nível de CD105 mais alto nos indivíduos que submetidos a quimioterapia (4,43 ng/ml); Em contrapartida, encontrou-se um nível de FCEV mais baixo em indivíduos que submetidos a quimioterapia (543,65 pg/ml). Houve uma diferença estatisticamente significativa nos níveis de CD105 (p = 0,003) e de FCEV (p = 0,002) entre os indivíduos submetidos e não submetidos à terapia com bevacizumabe. Os níveis de CD105 foram mais elevados em indivíduos submetidos à terapia com bevacizumab (5,11 ng/ml); em contraste, observou-se um nível de FCEV mais alto em indivíduos que não foram submetidos à terapia com bevacizumabe (645,92 pg/ml). Houve uma correlação positiva significativa entre CD105 e FCEV em indivíduos que não receberam bevacizumabe (p < 0,01).
Conclusão Os resultados deste estudo corroboram a hipótese de “mecanismo de escape” na falha da terapia anti-angiogênica (anti-FCEV).
Publication History
Received: 11 August 2020
Accepted: 07 September 2020
Article published online:
24 May 2021
© 2021. Sociedade Brasileira de Coloproctologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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References
- 1 Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017; 66 (04) 683-691
- 2 Arjaans M, Schröder CP, Oosting SF, Dafni U, Kleibeuker JE, de Vries EG. VEGF pathway targeting agents, vessel normalization and tumor drug uptake: from bench to bedside. Oncotarget 2016; 7 (16) 21247-21258
- 3 Van Cutsem E, Cervantes A, Adam R. et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 2016; 27 (08) 1386-1422
- 4 Engstrom PF, Arnoletti JP, Benson III AB. et al; National Comprehensive Cancer Network. NCCN Clinical practice guidelines in oncology: colon cancer. J Natl Compr Canc Netw 2009; 7 (08) 778-831
- 5 Gacche RN. Compensatory angiogenesis and tumor refractoriness. Oncogenesis 2015; 4 (06) e153
- 6 Rapisarda A, Melillo G. Role of the VEGF/VEGFR axis in cancer biology and therapy. Adv Cancer Res 2012; 114: 237-267
- 7 Rosen LS, Gordon MS, Robert F, Matei DE. Endoglin for targeted cancer treatment. Curr Oncol Rep 2014; 16 (02) 365
- 8 Fonsatti E, Altomonte M, Arslan P, Maio M. Endoglin (CD105): a target for anti-angiogenetic cancer therapy. Curr Drug Targets 2003; 4 (04) 291-296
- 9 Takahashi N, Kawanishi-Tabata R, Haba A. et al. Association of serum endoglin with metastasis in patients with colorectal, breast, and other solid tumors, and suppressive effect of chemotherapy on the serum endoglin. Clin Cancer Res 2001; 7 (03) 524-532
- 10 Paauwe M, Heijkants RC, Oudt CH. et al. Endoglin targeting inhibits tumor angiogenesis and metastatic spread in breast cancer. Oncogene 2016; 35 (31) 4069-4079
- 11 Seon BK, Haba A, Matsuno F. et al. Endoglin-targeted cancer therapy. Curr Drug Deliv 2011; 8 (01) 135-143
- 12 Folkman J. What is the evidence that tumors are angiogenesis dependent?. J Natl Cancer Inst 1990; 82 (01) 4-6
- 13 Nakamura I, Shibata M, Gonda K. et al. Serum levels of vascular endothelial growth factor are increased and correlate with malnutrition, immunosuppression involving MDSCs and systemic inflammation in patients with cancer of the digestive system. Oncol Lett 2013; 5 (05) 1682-1686
- 14 Li C, Gardy R, Seon BK. et al. Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis. Br J Cancer 2003; 88 (09) 1424-1431
- 15 Minhajat R, Mori D, Tokunaga O. et al. Anti-CD105 Inhibits Primary Cancer Growth and Secondary Hematogenous Metastasis in a Xenograft Model. Vasc Dis Prev 2009; 6: 91-96
- 16 Minhajat R, Mori D, Yamasaki F, Sugita Y, Satoh T, Tokunaga O. Endoglin (CD105) expression in angiogenesis of colon cancer: analysis using tissue microarrays and comparison with other endothelial markers. Virchows Arch 2006; 448 (02) 127-134
- 17 Azzariti A, Porcelli L, Brunetti O. et al. Total and not bevacizumab-bound vascular endothelial growth factor as potential predictive factors to bevacizumab-based chemotherapy in colorectal cancer. World J Gastroenterol 2016; 22 (27) 6287-6295
- 18 Aoyagi Y, Iinuma H, Horiuchi A, Shimada R, Watanabe T. Association of plasma VEGF-A, soluble VEGFR-1 and VEGFR-2 levels and clinical response and survival in advanced colorectal cancer patients receiving bevacizumab with modified FOLFOX6. Oncol Lett 2010; 1 (02) 253-259