Correlation of Wnt antagonist sFPR1, Slug and β-catenin with prognosis and metastasis in colorectal carcinoma

Abstract

sFPR1 plays an important role in colorectal carcinoma (CRC) tumorigenesis, Slug is also considered to be related to the development of CRC. However, the relationship between them and the mechanism of their involvement in CRC metastasis remain unknown. In this study, immunohistochemistry (IHC) was used to detect the expression of sFPR1, β-catenin, and Slug in 145 samples of CRC and corresponding surrounding "normal" mucosa tissues. Furthermore, clinicopathological features such as age, sex and so on were also collected retrospectively. Western blot and Transwell were used to detect proteins expression and migration capacity. In present study, the expression of sFPR1, Slug and β-catenin proteins were significantly correlated with lymph node metastasis and tumor-node-metastasis (TNM) stage of patients with CRC. sFPR1 expression showed a negative correlation with Slug and β-catenin. Kaplan-Meier analysis indicated that the postoperative 5-year OS of patients was related to the expression of sFPR1 and Slug, multivariate Cox regression analysis revealed that sFPR1 expression was an independent prognostic factor for CRC patients. Moreover, we found that the expression of slug and β-catenin could be regulated by sFPR1 in SW480 cells, and migration capacity of SW480 cells was suppressed with sFPR1 restoration. In summary, our data suggest that sFRP1, Slug and β-catenin are related to metastasis and prognosis in CRC. sFPR1 could mediate CRC metastasis by regulating the expression of Slug and β-catenin. Combined detection of these factors may be of significant value in predicting the metastasis and prognosis in CRC patients.

Keywords: CRC; metastasis; prognosis; sFPR1; slug; β-catenin.

Figure 1

Expression of the proteins in colorectal carcinoma (×400 magnification). A. Positive sFPR1 expression in the cytoplasm of “normal” mucosa cells. B. Positive sFPR1 expression in the cytoplasm of cancer cells. C. Positive Slug expression in the cytoplasm of “normal” mucosa cells. D. Positive Slug expression in the cytoplasm of cancer cells. E. Positive β-catenin expression in the membrane of “normal” mucosacells. F. Positive β-catenin expression in the membrane of cancer cells. G. Positive β-catenin expression in the nucleus of cancer cells. H. Positive β-catenin expression in the nucleus and cytoplasm of cancer cells.

Figure 2

Kaplan-Meier analysis of the survival rate of patients with colorectal carcinoma. (A) Overall survival of all patients in relation to sFPR1 expression (log-rank = 17.415, P < 0.001). (B) Overall survival of all patients in relation to β-catenin expression (log-rank = 21.387, P < 0.001). (C) Overall survival of all patients in relation to Slug expression (log-rank = 10.415, P = 0.001). In (A-C) analyses, the green line represents positive expression of proteins and the blue line represents negative expression of proteins. (D) Overall survival of all patients in relation to the combination of sFPR1, β-catenin and Slug expression (log-rank = 34.157, P < 0.001). The green line represents positive expression of sFRP1 and negative expression of Slug, β-catenin and the blue line represents negative expression of sFRP1 and positive expression of Slug, β-catenin. The red line represents other positive or negative expression of the proteins. In all analyses, †represents censored observation.

Figure 3

The expression of sFPR1, β-catenin and Slug was determined by Western blotting in the SW480 cell line treated with 5-aza-dc.

Figure 4

The migration capacity of SW480 cells treated with 5-aza-dC was detected by transwell assay. P < 0.05.