Profiles of Endoglin and Vascular Endothelial Growth Factor Based on Staging and Histological Grading of Colorectal Cancer and Their Relationship with Bevacizumab Therapy

Minhajat, Rahmawati; Saleh, Sahyuddin; Harjianti, Tutik; Benyamin, Andi Fachruddin; Parewangi, A. M. Luthfi; Bakri, Syakib

doi:10.1055/s-0041-1724065

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Journal of Coloproctology (Rio de Janeiro)

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Original Article • J. Coloproctol. (Rio J.) 41 (02) • Apr-Jun 2021 • https://doi.org/10.1055/s-0041-1724065 copy

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 coma terapia com bevacizumabe

Authorship SCIMAGO INSTITUTIONS RANKINGS

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 enzymelinked 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). Therewas 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).

Keywords:
angiogenesis; bevacizumab; colorectal adenocarcinoma; CD105; VEGF

Variable	Category	n	%
Gender	Male	48	54.5
Gender	Female	40	45.5
Age	20–49 years old	32	36.4
	50–59 years old	21	23.9
	60–77 years old	35	39.8
Tumor location	Ascending colon	15	17.0
	Transversal colon	3	3.4
	Descending colon	16	18.2
	Rectosigmoid	26	29.5
	Rectum	28	31.8
Metastasis	Yes	54	61.4
Metastasis	No	34	38.6
Staging	I	19	21.6
	II	15	17.1
	III	11	12.5
	IV	43	48.9
Grading histology	Well-differentiated	29	33.0
	Moderate	39	44.3
	Poor	16	18.2
	Mucinous	4	4.5
Chemotherapy	Yes	51	58
Chemotherapy	No	37	42
Chemotherapy + Bevacizumab	Yes	18	35.3
Chemotherapy + Bevacizumab	No	33	64.7

Variable	Minimum	Maximum	Mean	SD
CD105 (ng/ml)	1.69	7.55	4.25	1.37
VEGF (pg/ml)	20.21	2,758.89	610.21	583.20

Variable	Metastasis	n	Mean	SD	p-value
CD105 (ng/ml)	Yes	54	4.59	1.35	0.002^* * Mann-Whitney test.
CD105 (ng/ml)	No	34	3.71	1.24	0.002^* * Mann-Whitney test.
VEGF (pg/ml)	Yes	54	650.27	635.58	0.625^* * Mann-Whitney test.
VEGF (pg/ml)	No	34	546.58	491.01	0.625^* * Mann-Whitney test.

Variable	Chemotherapy	n	Mean	SD	p-value
CD105 (ng/ml)	Yes	51	4.43	1.42	0.038^* * Kruskal-Wallis test.
CD105 (ng/ml)	No	37	4.00	1.25	0.038^* * Kruskal-Wallis test.
VEGF (pg/ml)	Yes	51	543.65	400.58	0.010^* * Kruskal-Wallis test.
VEGF (pg/ml)	No	37	701.94	441.17	0.010^* * Kruskal-Wallis test.

Variable	Bevacizumab	n	Mean	SD	p-value
CD105 (ng/ml)	Yes	18	5.11	1.30	0.003^* * Mann-Whitney test.
CD105 (ng/ml)	No	33	4.06	1.38	0.003^* * Mann-Whitney test.
VEGF (pg/ml)	Yes	18	356.16	589.19	0.002^* * Mann-Whitney test.
VEGF (pg/ml)	No	33	645.92	565.91	0.002^* * Mann-Whitney test.

Variable	Histological grading	n	Mean	SD	p-value
CD105 (ng/ml)	Well-differentiated Differentiation	29	3.95	1.40	0.009^* * Kruskal-Wallis test.
	Moderate Differentiation	39	4.16	1.37
	Poor Differentiation	16	5.17	0.92
	Mucinous	4	3.59	1.47
VEGF (pg/ml)	Well-differentiated Differentiation	29	511.77	513.84	0.025^* * Kruskal-Wallis test.
	Moderate Differentiation	39	565.95	636.46
	Poor Differentiation	16	909.47	567.85
	Mucinous	4	558.31	235.74

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[1] Address for correspondence Rahmawati Minhajat, MD, PhD, Divisi Hematologi Onkologi Medik Departemen Ilmu Penyakit Dalam, Fekultas Kedokteran Universitas Hasanuddin, Rumah Sakit UNHAS Gedung A Lantai 5, Jl. Perintis Kemerdekaan Km.11, Tamalanrea, Makassar-Indonesia (e-mail: rahmawati.minhajat@gmail.com).