Endoglin (CD105) and VEGF as potential angiogenic and dissemination markers for colorectal cancer

Abstract

Background: Colorectal cancer (CRC) is an important current problem concerning public health due to its high incidence and mortality. Advances in molecular and cellular knowledge and the detection of new disease biomarkers are very important to improve prognosis, prediction, and early diagnosis. In this study, we aimed to analyze the gene and protein expression levels of two angiogenic markers, VEGF and soluble Endoglin, during different tumor stages as well as at different stages of cancer treatment, to predict the diagnosis and evolution of colon and rectal cancer. Material and methods: This study includes 133 CRC patients (93 with colon cancer and 40 with rectal cancer) on which the gene and protein expression of Endoglin (membrane and soluble form) and VEGF were analyzed by molecular and immunohistochemical techniques on different tumor stage samples and plasma obtained preoperatively as well as 3, 6, and 9 months after resection of the tumor. Results: VEGF and Endoglin gene expressions were higher in tumor tissue than in surrounding non-tumoral tissue for both types of cancer. The VEGF levels in plasma were found to decrease in less aggressive tumors, whereas soluble Endoglin was increased in preoperative samples of patients with metastasis. Membrane Endoglin expression was higher on the vascular endothelium of more aggressive tumors. In contrast, Endoglin expression was mainly in the colon epithelium in less aggressive stage tumors. Conclusion: Endoglin and VEGF are proteins with a major role in the tumor angiogenesis process. This study performed with a wide cohort of human samples shows that both proteins seem to be valuable biomarkers in the diagnosis and prognosis of CRC.

Expressions of TWIST1 and CD105 markers in colorectal cancer patients and their association with metastatic potential and prognosis

“…In addition, our finding exhibited that endothelial CD105 expression was higher in CRC tissues compared to adjacent normal tissues, which is in line with the results of a study by Zeljko et al [55]. Besides, we observed and noticed of CD105 expression in tumor cells, while very few studies have reported cytoplasmic CD105 in tumor cells of CRC patients [27]. Data analysis also showed a statistically significant association between cytoplasmic of CD105 expressions of tumor cells and TNM stage in CRC patients.…”

“…Stage IV, as the most advanced stage that occurred distant metastasis, was a higher level of tumoral cytoplasmic CD105 expression in comparison with a lower stage II that showed the association of cytoplasmic CD105 expression in tumor cells with tumor aggressiveness in CRC. In a recent study, cytoplasmic expression of CD105 in tumor cells was observed in the samples of less aggressive colon cancer [27], while CD105 expression in tumor cells was correlated with the advanced tumor stage of kidney and ovarian cancers [25,56]. We have also observed a positive significant correlation between CD105 expression in two different cells (endothelial cells and cytoplasm of tumor cells) in CRC tissues.…”

“…CD105 contributes to all malignancies, which can be upregulated by hypoxia and TGF-βs; therefore, it can help in promoting tumor proliferation and metastasis in several types of cancer [22][23][24]. Studies have shown that overexpression of endothelial CD105 is associated with the advanced cancer, so CD105 can be considered as a prognosis marker and as a targeted therapy [25][26][27]. Also, the increased expression of CD105 was observed in aggressive and metastatic CRC patients [14,28].…”

Differences of Angiogenesis Factors in Tumor and Diabetes Mellitus

“…It is also used in 133 patients with Colorectal cancer by ELISA of soluble Endoglin and VEGF, immunohistochemistry, total RNA extraction, cDNA synthesis, and quantitative real-time PCR proved that it was closely related to tumor angiogenesis. 73 In diabetes, glucose, directly and indirectly, stimulates the expression of VEGF-A in podocytes through TGF-β, and the increase of VEGF-A inhibits the expression of TGF-β, which is a negative feedback mechanism. 21…”

Serum Soluble Endoglin Versus Serum Placental Growth Factor for Early Prediction of Preeclampsia

“…Endoglin (Eng) is expressed as a 180-kDa membrane-bound homodimer formed by disulfide-linked monomers from a gene that was localized to chromosome 9q34ter [9] . Eng is responsible for adequate angiogenesis and vascular remodeling as evidenced by animal studies that proved embryonic death due to defective angiogenesis in animal lacking gene for Eng [10] , also Eng gene was found to be mutated in patients with hereditary hemorrhagic telangiectasia type 1 [11] and endoglin plays a major role in tumoral and nontumoral adult angiogenesis [12] . Soluble endoglin (sEng) is the circulating form of Eng that was produced by proteolytic processing of membrane Eng [13] .…”