The correlation between expression of E-cad and VEGF and lymph node metastasis was analyzed. As shown in Table 3, the positive expression of E-cad decreased with the increase of the number of lymph node metastasis. In the cases without lymph node metastasis, the expression of E-cad was 55.6% in Han and 56.3% in Uygur. In the case with lymph node metastasis, especially the number of metastases ≥4, the positive expression of E-cad was only 32.1% in Han and 21.3% in Uygur. There was a negative correlation between the E-cad and lymph node metastasis (−1≤r < 1, P < .05). With the number of lymph node metastasis increased, positive expression of VEGF gradually increased. When the number of lymph node metastases was ≥4, the positive expression of VEGF was 71.4% in Han and 73.7% in Uygur, respectively. There was a positive correlation between the VEGF and lymph node grouping (−1≤r < 1, P < .05). These results indicate that lymph node metastasis is related to the loss of E-cad and the overexpression of VEGF in TNBC patients.
The expression and correlation of E-cad and VEGF in different TNM stages were statistically analyzed in Han and Uygur women TNBC patients. The results showed that the expression of E-cad and VEGF in the TNM staging of TNBC were significantly different (P < .05) (Table 4). In both groups, the positive expression of E-cad in stage I was higher than that in stage II and III, whereas the positive rate of VEGF in stage III was higher than that in stage I and II. Correlation analysis showed that the expression of E-cad decreased gradually with the TNM clinical stage increased (P < .05), and the difference was statistically significant (−1≤r < 1, P < .05). Statistically, the positive rate of VEGF was gradually increased with the increase of TNM clinical stage (0 < r < 1, P < .05). These results demonstrate that TNM staging correlates with the loss of E-cad and the overexpression of VEGF in TNBC patients.
The expression and correlation of E-cad and VEGF in different histological grades were statistically analyzed in Han and Uygur women TNBC patients. The results are shown in Table 5. The results showed that the expression of E-cad in the Han and Uygur women were negatively correlated with histological grading (−1 ≤ r < 1, P < .05). With the increase of histological grade, loss of E-cad expression was more obvious. There was no significant correlation between the expression of VEGF and the histological grading (P > .05). These results show that histological grading is associated with the loss of E-cad, but not with the overexpression of VEGF in TNBC patients.
All patients were followed up regularly. Until December 2016, there were 44 (44/172, 25.6%) and 26 (26/79, 32.9%) case of TNBC patients with recurrence and metastasis in Han and Uighur, respectively. There was no significant difference between the 2 groups in the 5-year disease-free survival (Log rank = 1.566, P = .211) (Fig. 2).
Occurrence and development of breast cancer is related to genetic and environmental factors. Compared with N-TNBC, TNBC has complex molecular characteristics with different clinical and pathological features and prognosis.[1,2] There are significant differences in molecular characteristics of TNBC among different ethnic groups.[11,12] However, the clinical reports on TNBC are limited to the Han patients and there is a lack of control research among different ethnic groups. In this article, the expression levels of E-cad and VEGF, and their relationship with clinical characteristics of TNBC patients were investigated.
E-cad, a cell adhesion molecule, has a transmembrane glycoprotein structure distributed in 3 different regions of extracellular, transmembrane, and intracellular domain, which plays a role in signal transduction. E-cad plays a key role in cell movement and the process of epithelial-mesenchymal transition and migration during tumor invasion. The lack of E-cad expression is critical for epithelial tumor invasion and metastasis. Studies have shown that low expression of E-cad is a sign of poor tumor prognosis, and is significantly related to disease-free survival.[19,20] In this study, the results showed that 78 cases of patients had positive expression of E-cad in 172 cases of Han patients with the positive rate of 45.3%, and 30 cases of patients had positive expression of E-cad in 79 cases of Uygur patients with the positive rate of 38.0%. There was no significant difference between the 2 groups. These results suggest that there is no significant difference in expression of E-cad in TNBC patients of different ethnic groups.
VEGF can stimulate vascular endothelial cell proliferation and promote neovascularization of tumor cells. It is closely related to tumor growth. Studies have shown that the high expression of VEGF and 5-year disease-free survival rate is significantly related in TNBC patients and overexpression of VEGF corresponds to poor prognosis.[21,22] VEGF may become a new target for TNBC therapy. The combination of bevacizumab (anti-VEGF), epirubicin, cyclophosphamide, and docetaxel have increased the rate of pathologic remission in TNBC patients from 27.9% to 39.3%. Our results showed that the positive rate of VEGF expression in Han patients was significantly lower than that in Uygur patients. The reason for this difference may be because Uighur TNBC patients usually go to treatment at a late stage. This requires further study to confirm.
Through the follow-up, we found that the number of recurrence and metastasis was 44 cases (26.6%) and 26 cases (32.9%) in Han and Uygur TNBC patients, respectively, without significant difference. There was no significant difference in 5-year disease-free survival between 2 groups.
Study has shown that the invasion of tumor cells and expression levels of E-cad are negatively correlated. By overexpression of E-cad, the invasion of tumor cells can be effectively inhibited. E-cad plays an important role in the development and progression of TNBC and can be used as a prognostic indicator of TNBC.[19,27] In this study, we found that the expression of E-cad was negatively correlated with the lymph node status, TNM staging, and histological grading in both the Han and Uygur groups. With the increased number of lymph node metastasis, the later clinical stage, the higher histological grade, lack of E-cad expression is more obvious, which affects the prognosis of patients with TNBC. The 5-year overall survival and disease-free survival rates of E-cad-negative patients with 61% and 27% were significantly lower than those of E-cad-positive patients with 89% and 65%, respectively.
Overexpression of VEGF in TNBC has correlation with lymph node metastasis and tumor stage, and is prone to cause early recurrence and metastasis of TNBC and poor prognosis. A study of TNBC recurrence has shown that the expression of VEGF is significantly different in different stages of TNBC. In 2011, Song et al showed HIF1a, VEGF related to Wnt, and β-catenin and in patients with AML, but the mechanism has not been investigated. Our study showed that the positive expression rate of VEGF was positively correlated with the number of lymph node metastasis and TNM staging in Han and Uygur TNBC patients, but not the histological grading, which was consistent with previous report. With the increased number of lymph node metastasis and TNM stage, the positive expression of VEGF gradually increased, indicating that VEGF plays a certain role in the progress of TNBC.
Lymph node metastasis, TNM staging, and histological grading are important basis for clinical judgment of prognosis and reference clues for development of individualized comprehensive treatment program. The correlation of E-cad and VEGF with lymph node metastasis, TNM stage, and histological grade further suggests that we should pay great attention to the differences of E-cad and VEGF expression in different ethnic TNBC patients. E-cad and VEGF may have clinical significance as therapy targets. Individual treatment strategies for TNBC patients of different ethnic groups should be taken to obtain a higher cure rate and survival rate.
In conclusion, we reported that the 5-year disease-free survival rate of TNBC patients in Han and Uygur patients had no significant difference, but the difference of VEGF expression rate was statistically significant, indicating that VEGF could be used as an independent factor in the prognosis of TNBC. With the increase of VEGF expression, the prognosis is worse. Meanwhile, this study also showed that the positive expression rate of VEGF in Uygur TNBC patients was higher than that in Han patients, but the 5-year disease-free survival rate and expression of E-cad were not significantly different. In the prognosis of N-TNBC, it has been demonstrated that the 6-year disease-free survival rate of Uygur Lumina A breast cancer patients is lower than that of Han patients. Therefore, these results suggest that the prognosis factors of Uygur TNBC patients may be different from those of Han TNBC patients.
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