The prognostic significance of lysosomal protective protein (cathepsin A) in breast ductal carcinoma in situ

Abstract

Aims Cathepsin A (CTSA) is a key regulatory enzyme for galactoside metabolism. Additionally, it has a distinct proteolytic activity and plays a role in tumour progression. CTSA is differentially expressed at the mRNA level between breast ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IBC). In this study, we aimed to characterise CTSA protein expression in DCIS and evaluate its prognostic significance. Methods and results A large cohort of DCIS [n = 776 for pure DCIS and n = 239 for DCIS associated with IBC (DCIS/IBC)] prepared as a tissue microarray was immunohistochemically stained for CTSA. High CTSA expression was observed in 48% of pure DCIS. High expression was associated with features of poor DCIS prognosis, including younger age at diagnosis (<50 years), higher nuclear grade, hormone receptor negativity, HER2 positivity, high proliferative index and high hypoxia inducible factor 1 alpha expression. High CTSA expression was associated with shorter recurrence‐free interval (RFI) (P = 0.0001). In multivariate survival analysis for patients treated with breast conserving surgery, CTSA was an independent predictor of shorter RFI (P = 0.015). DCIS associated with IBC showed higher CTSA expression than pure DCIS (P = 0.04). In the DCIS/IBC cohort, CTSA expression was higher in the invasive component than the DCIS component (P < 0.0001). Conclusion CTSA is not only associated with aggressive behaviour and poor outcome in DCIS but also a potential marker to predict co‐existing invasion in DCIS.

Renin angiotensin system genes are biomarkers for personalized treatment of acute myeloid leukemia with Doxorubicin as well as etoposide

“…Similar to our findings, low expression of IGF2R in nonsmall cell liver cancer has been associated with poor prognosis and high expression in bladder cancer has been associated with good prognosis [57,58]. Although high CTSA expression was associated with poorer outcome in breast ductal carcinoma in situ, it was also found to suppress invasion and metastasis of colorectal cancer, suggesting tissue-specific differential roles [59,60]. Recent studies linked ATP6AP2 up-regulation to the progression of glioma and colorectal cancer, due to its roles in aberrant activation of the Wnt/beta-catenin signalling pathway [61,62].…”

Predictive value of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) in patients with oesophageal cancer undergoing concurrent chemoradiotherapy

“…Among the many potential biomarkers, such as genetic, immunological, and haematological markers, systemic inflammatory markers in peripheral blood are receiving increasing attention for prediction of tumour recurrence, metastasis, and prognosis [16–18]. Recent studies have shown that absolute inflammatory cell counts in peripheral blood (neutrophils, white blood cells, lymphocytes and monocytes) and ratios based on these cell counts (NLR, PLR and LMR) may play a key role in predicting the overall survival of patients with tumours, including colorectal cancer [19], head and neck cancer [20], non-small cell lung cancer [21].…”

Prognostic significance and oncogene function of cathepsin A in hepatocellular carcinoma

“…Cathepsin A (CTSA) is a renowned serine protease cathepsin member of the cathepsin lysosomal protease family, which with a role in protecting β-galactosidase and neuraminidase-1 from intra-lysosomal proteolysis 19 . In recent years, CTSA overexpression has been observed in various types of human cancers such as breast cancer, lung cancer, and prostate cancer 20 – 23 . CTSA also has been identified as a potential biomarker for early diagnosis, prognosis and monitoring during cancer treatment.…”