Down regulation of ADAM33 as a Predictive Biomarker of Aggressive Breast Cancer

Abstract

Breast cancer is a heterogeneous disease with differences in its clinical, molecular and biological features. Traditionally, immunohistochemical markers together with clinicopathologic parameters are used to classify breast cancer and to predict disease outcome. Triple-negative breast cancer (TNBC) is a particular type of breast cancer that is defined by a lack of expression of hormonal receptors and the HER2 gene. Most cases of TNBC also have a basal-like phenotype (BLBC) with expression of cytokeratin 5/6 and/or EGFR. A basal marker alone is insufficient for a better understanding of the tumor biology of TNBC. In that regard, the ADAM33 gene is silenced by DNA hypermethylation in breast cancer, which suggests that ADAM33 might be useful as a molecular marker. In the present study, we have produced monoclonal antibodies against the ADAM33 protein and have investigated the role of ADAM33 protein in breast cancer. We used 212 breast tumor samples and lower levels of ADAM33 were correlated with TNBC and basal-like markers. A lower level of ADAM33 was also correlated with shorter overall survival and metastasis-free survival and was considered an independent prognostic factor suggesting that ADAM33 is a novel molecular biomarker of TNBC and BLBC that might be useful as a prognostic factor.

Long Non-Coding RNA (LncRNA) HOXA11-AS Promotes Breast Cancer Invasion and Metastasis by Regulating Epithelial-Mesenchymal Transition

“…If non-metastatic and primary breast cancer is found early and surgically treated in time, patient 5-year and 10-year survival rates are higher [ 25 ]. However, for metastatic, secondary, and recurrent breast cancer, surgery alone cannot inhibit cancer cell spread and tumor regeneration because of the metastasis of tumor cells, and even though the operation is combined with chemotherapy, radiotherapy, and molecular targeting treatment to treat metastatic breast cancer, its efficacy is also limited [ 26 ].…”

The regulatory roles and mechanisms of the transcription factor FOXF2 in human diseases

“…Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among females worldwide, especially in developed countries ( Torre et al, 2015 ). The top two aggressive types of breast cancer are BLBC and triple-negative breast cancer (TNBC), which have similar tissue morphology, immunophenotypes, and gene expression profiles ( Manica et al, 2017 ). FOXF2 is specifically expressed in TNBC/BLBC and has lower expression in luminal and HER2+ breast cancers ( Lo et al, 2016 ).…”

Importance of predictive biomarkers related to Pharmacogenetics in breast cancer and prostate: a systematic review

“…Breast cancer is a prevalent malignancy in the female population, as it is a complex disease, several factors interfere with the prognosis and the outcome of a specific therapeutic regimen. Each type of breast cancer has a different behavior, precisely because these neoplastic cells express hormone receptors (estrogen and / or progesterone) and HER2 protein, causing the cancer to vary its way of tumor progression (Manica et al, 2017). The present study was therefore conducted by analyzing the status of different predictive factors in breast carcinoma subtypes, elucidating the correlations of these factors, in order to identify significant relationships between the types of breast cancer.…”