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.

Autophagy activation, lipotoxicity and lysosomal membrane permeabilization synergize to promote pimozide- and loperamide-induced glioma cell death

“…Of note, lysosomal function is often upregulated in cancer cells to fulfill increased metabolic demands, and elevated cathepsin expression is associated with increased invasiveness and metastasis [58][59][60][61]. This high dependence on the lysosomal pathway paired with decreased stability of cancer cell lysosomes (e.g.…”

Cathepsin K associates with lymph node metastasis and poor prognosis in oral squamous cell carcinoma

“…The pathophysiological role of the cathepsins in cancer metastasis has attracted the interest of studying its value as a biomarker of metastasis and prognosis in various types of malignancy. Increased protein expression of cathepsins V, B and D has been associated with distant metastasis and worse DSS in breast cancer [ 22 ]. Similar results have been found for cathepsin A in malignant melanoma and cathepsin B in non-small cell lung carcinoma [ 23 , 24 ] and in OSCC [ 11 – 14 ].…”

A Novel Strategy to Investigate Tissue‐Secreted Tumor Microenvironmental Proteins in Serum toward Development of Breast Cancer Early Diagnosis Biomarker Signature

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