Expression profile of cathepsins indicates the potential of cathepsins B and D as prognostic factors in breast cancer patients

Abstract

Breast cancer is one of the most prevalent types of cancer in women and contributes to 32% of all female cancer cases. Cathepsins, a family of proteins, are known to have a critical role in human cancers. However, previous studies on the systematic analysis of the role of cathepsin family members in breast cancer are limited. The aim of the present study was to identify biological markers to predict prognosis and treatment response of breast cancer patients, as well as to elucidate novel therapeutic targets. The present study analyzed the expression of six members of cathepsin family, including cathepsins B, G, D, K, L and V in 188 breast cancer tissue specimens using immunohistochemistry. The data showed that all members of the tested cathepsin families featured cytoplasmic staining. Notably, expression of cathepsin L was associated with advanced tumor stages, while cathepsins B and K expression levels were associated with positive estrogen receptor expression; in addition, cathepsin K expression was also demonstrated to be associated with progesterone receptor expression. Cathepsins V and D expression levels were found to be associated with breast cancer metastasis, while the expression levels of cathepsins B and D were associated with poor disease-free survival in breast cancer patients. In addition, univariate analysis demonstrated that breast cancer metastasis to the bone and the expression of cathepsin B protein were associated with poor disease-free survival. In conclusion, the results of the present study indicated that the altered expression of cathepsins, in particular cathepsins B and D, contributed to the progression of breast cancer and poor disease-free survival in breast cancer patients.

Keywords: breast cancer; cathepsins; expression profile; prognosis.

Figure 1.

Detection of cathepsins B, D, G, K, L and V as well as RECK and VEGF proteins in breast cancer tissue specimens using immunohistochemistry. Representative images were selected to reflect the expression of (A and B) cathepsin B, (C and D) cathepsin C, (E and F) cathepsin D, (G and H) cathepsin K, (I and J) cathepsin L, (K and L) RECK, (M and N) cathepsin V expression and (O and P) VEGF in breast cancer tissues. Magnification, ×200. RECK, reversion-inducing cysteine-rich protein with Kazal motifs; VEGF, vascular endothelial growth factor.

Figure 2.

Association of cathepsin B, cathepsin D and VEGF expression in breast cancer tissues with disease-free survival of breast cancer patients. Kaplan-Meier curve of survival of patients according to (A) cathepsin B expression (P<0.001), (B) cathepsin D expression (P=0.050) and (C) VEGF expression (P=0.041). VEGF, vascular endothelial growth factor; Cum survival, cumulative survival; DDFS, distant disease-free survival; Cat., cathepsin; 0, low expression; 1, high expression.