Thrombin-activatable fibrinolysis inhibitor Thr325Ile polymorphism and plasma level in breast cancer: A pilot study

Abstract

This study aimed to investigate thrombin-activatable fibrinolysis inhibitor (TAFI) Thr325Ile polymorphism and TAFI antigen (Ag) levels in breast cancer (BC) in the Egyptian population to clarify their role in relation to BC. A group of 300 females was recruited in this study; of these 150 unrelated patients with different stages of BC and 150 age-matched healthy controls. Plasma TAFI Ag was measured by ELISA and TAFI Thr325Ile (rs1926447) polymorphism was genotyped using TaqMan single nucleotide polymorphism (SNP) genotyping assay. The results showed the genotypes of the minor allele; Thr/Ile (CT) and Ile/Ile (TT) were significantly more frequent in patients compared to control group (50.0% and 22.0% vs. 42.0% and 13.3%, respectively) and were also associated with BC susceptibility [OR = 1.9 and 2.6; 95% CI: (1.1–3.3) and (1.3–5.5), respectively P = 0.01]. Ile325 allele carriers were more frequent in cases than in controls (47.0% vs. 34.0%) [OR = 1.7, (95% CI = 1.2–2.4), P = 0.001]. However, TAFI Thr325Ile polymorphism was not associated with BC stage or other clincopathological characteristics. TAFI Ag levels were correlated with advanced stages of BC, poor prognosis and risk of recurrence (P = 0.02, P = 0.04 and P < 0.001, respectively) and Thr325Ile SNP was significantly correlated with TAFI antigen levels with the C/C genotype corresponding to the highest and the T/T genotype to the lowest TAFI antigen levels (P < 0.001) in the study groups. In conclusion, this study showed for the first time that TAFI Thr325Ile polymorphism could have a contribution to BC susceptibility in our population. Furthermore, high TAFI plasma levels may serve as a predictor of poor prognosis in patients with BC.

IL-10 correlates with the expression of carboxypeptidase B2 and lymphovascular invasion in inflammatory breast cancer: The potential role of tumor infiltrated macrophages

“…In the present study, we found that the incidence of CPB2 genotypes carrying the allele antigen [19]. We found the CPB2 mRNA expression was higher in breast carcinoma tissues as compared to normal breast tissues.…”

“…Since lymphovascular invasion is essential for metastasis, this suggests a role for pro-CPB2 in metastasis. Previous studies have shown an association between pro-CPB2 and metastasis in Chinese breast cancer patients [18], and with poor prognosis in Egyptian breast cancer patients [19].…”

“…A pilot study assessing pro-CPB2 level in plasma of Egyptian breast cancer patients showed an increase in pro-CPB2 plasma level that is correlated with advanced stages, poor prognosis and high risk of disease recurrence. Furthermore, CPB2 Thr325Ile polymorphism was associated with the development of breast cancer in Egyptian population [19].…”

Suppression of TAFI by siRNA inhibits invasion and migration of breast cancer cells

“…Reports showed that (12,13) databases indicate a high expression of TAFI levels in breast, ovarian and hepatic cancer cell lines. Plasma levels of TAFI are also increased in a number of types of cancers, including BC (10,29). In addition, higher levels of TAFI have been associated with more advanced stages of cancer (30).…”

“…Activation of TAFI by thrombin is increased 1,250-fold in the presence of the endothelial cell membrane protein thrombomodulin (TM) (7), which is expressed in tumors and is a prognostic factor in human cancer (8,9). Several studies have demonstrated that higher TAFI levels are associated with various types of cancer (10)(11)(12)(13), and plasma levels of TAFI are significantly increased in breast and lung cancer, gastric carcinoma and multiple myeloma compared with healthy individuals, suggesting that TAFI may serve a role in the pathogenesis of thrombotic disorders in cancer patients (14,15). However, the role of TAFI in tumor development remains to be fully elucidated.…”