Overexpression of δ-catenin is associated with a malignant phenotype and poor prognosis in colorectal cancer

Abstract

Little is known regarding the expression or clinical significance of δ-catenin, a member of the catenin family, in colorectal cancer (CRC). The present study examined the expression of δ-catenin using immunohistochemistry in 110 cases of CRC, including 70 cases with complete follow‑up records and 40 cases with paired lymph node metastases. In addition, δ‑catenin mRNA and protein expression were compared in 30 pairs of matched CRC and normal colorectal tissues by reverse transcription quantitative polymerase chain reaction and western blot analysis. δ‑Catenin was weakly expressed or absent in the cytoplasm of normal intestinal epithelial cells, whereas positive δ‑catenin expression localized to the cytoplasm was observed in CRC cells. The rate of positive δ‑catenin expression in CRC (68.18%; 75/110) was significantly higher than that in normal colorectal tissues (36.7%; 11/30; P<0.001). In addition, δ‑catenin mRNA and protein expression were significantly increased in CRC tissues compared to those in their matched normal tissues (all P<0.05). The expression of δ‑catenin in stage III‑IV CRC was higher than that in stage I‑II CRC, and the expression of δ‑catenin in the tumors of patients with lymph node metastases was higher than that in patients without lymph node metastases. Kaplan‑Meier survival curves demonstrated that the survival time of patients with positive δ‑catenin expression was shorter than that of patients with negative δ‑catenin expression (P=0.005). Furthermore, Cox multivariate analysis indicated that the tumor, nodes and metastasis stage (P=0.02) and positive δ-catenin expression (P=0.033) were independent prognostic factors in CRC. The present study therefore indicated that δ-catenin may be a suitable independent prognostic factor for CRC.

Figure 1

Immunohistochemical staining for δ-catenin in normal colorectal tissues and colorectal cancer tissues. (A) Weak expression of δ-catenin was observed in the cytoplasm of normal colorectal gland epithelial cells. Scale bar, 50 µm. (B and C) Obviously enhanced expression of δ-catenin was observed in (B) the cytoplasm of poorly differentiated colorectal cancer cells and (C) highly differentiated colorectal cancer cells. (D) The expression of δ-catenin was also higher in lymph node metastases, compared to the corresponding primary tumor foci in C. Magnification, ×400.

Figure 2

δ-Catenin has a prognostic value in colorectal cancer. Kaplan-Meier survival curves for colorectal cancer patients stratified by the expression of δ-catenin. The mean survival time and five-year survival rate for colorectal cancer patients with positive δ-catenin expression (blue solid line; n=45) were significantly lower than those of patients with negative δ-catenin expression (green dashed line; n=25; P=0.005).

Figure 3

Reverse transcription quantitative polymerase chain reaction analysis of δ-catenin mRNA expression in colorectal cancer tissues. δ-Catenin mRNA expression was significantly higher in colorectal cancer tissues than the matched normal colorectal tissues. The horizontal solid lines indicate the median value in each group. In the bar graph, values are expressed as the mean ± standard deviation. ^***P<0.0001 (n=30). T, tumor tissue; N, normal tissue.

Figure 4

Correlation between δ-catenin mRNA expression and the clinicopathological features of 30 colorectal cancer patients. The horizontal solid lines indicate the median value in each group. ^*P-values were calculated using the non-parametric Mann-Whitney test or Kruskal-Wallis test. TNM, tumor, nodes, metastasis stage.

Figure 5

Western blot analysis of δ-catenin protein expression in colorectal cancer tissues. δ-Catenin protein expression was significantly higher in colorectal cancer tissues than that in the matched normal colorectal tissues. Values are expressed as the mean ± standard deviation. ^***P<0.0001 (n=30). T, tumor tissue; N, normal tissue.