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HERG1 channel expression associates with molecular subtypes and prognosis in breast cancer.

ABSTRACT: Background:Breast cancer (BC) is the most frequent malignancy among females worldwide. Despite several efforts and improvements in early diagnosis and treatment, there are still tumors characterized by an aggressive behavior due to unfavorable biology, thus quite difficult to treat. In this view, searching for novel potential biomarkers is mandatory. Among them, in the recent years data have been gathered addressing ion channel as important players in oncology. Methods:A retrospective pilot study was performed on 40 BC samples by means of immunohistochemistry in order to evaluate hERG1 potassium channels expression in BC. Results:We provide evidence that hERG1 is expressed in all the BC samples analyzed. hERG1 expression was significantly associated with molecular subtype with the highest expression in Luminal A and the lowest in basal-like tumors (p?=?0.001), tumor grading (the highest hERG1 expression in well-moderate differentiated tumors, p?=?0.020), estrogen receptors (high hERG1 expression in ER-positive samples, p?=?0.008) and Ki67 proliferative index (high hERG1 scoring in samples with low proliferative index, p?=?0.038). Also, a p value close to significance was noticed for the association between hERG1 and HER2 expression (p?=?0.079). At the survival analysis, patients with high hERG1 expression turned out to have a longer progression-free survival, although statistical significance was not reached (p?=?0.195). The same trend was observed analyzing local relapse free-survival (LRFS) and metastases-free survival (MFS): patients with higher hERG1 scoring had longer LRFS and MFS (p?=?0.124 and p?=?0.071, respectively). Conclusions:The results of this pilot study provide the first evidence that the hERG1 protein is expressed in primary BC, and its expression associates with molecular subtype. hERG1 apparently behaves as a protective factor, since it contributes to identify a subset of patients with better outcome. Overall, these data suggest that hERG1 might be an additional tool for the management of BC, nevertheless further investigations are warranted to better clarify hERG1 role and clinical usefulness in BC.

SUBMITTER: Iorio J

PROVIDER: S-EPMC6034270 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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hERG1 channel expression associates with molecular subtypes and prognosis in breast cancer.

Iorio Jessica J Meattini Icro I Bianchi Simonetta S Bernini Marco M Maragna Virginia V Dominici Luca L Casella Donato D Vezzosi Vania V Orzalesi Lorenzo L Nori Jacopo J Livi Lorenzo L Arcangeli Annarosa A Lastraioli Elena E

Cancer cell international 20180705

<h4>Background</h4>Breast cancer (BC) is the most frequent malignancy among females worldwide. Despite several efforts and improvements in early diagnosis and treatment, there are still tumors characterized by an aggressive behavior due to unfavorable biology, thus quite difficult to treat. In this view, searching for novel potential biomarkers is mandatory. Among them, in the recent years data have been gathered addressing ion channel as important players in oncology.<h4>Methods</h4>A retrospec ...[more]

PMID: 30002601

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Project description:BackgroundIn 2014, breast cancer remains a major cause of mortality worldwide mostly due to tumor relapse and metastasis. There is currently a great interest in identifying cancer biomarkers and signalling pathways mechanistically related to breast cancer progression. Matrix metalloproteinase-9 (MMP-9) is a member of matrix degrading enzymes involved in cancer development, invasion and metastasis. Our objective was to investigate MMP-9 expression in normal human breast tissue and to compare it to that of breast cancer of various histological grades and molecular subtypes. We also sought to correlate MMP-9 expression with the incidence of metastasis, survival rates and relapse in breast cancer patients.MethodsMMP-9 was first studied using in silico analysis on available DNA microarray and RNA sequencing data of human breast cancer tissues and human breast cancer cell lines. We next ascertained MMP-9 expression in both normal breast tissue and in human breast carcinoma tissue microarrays.ResultsSignificant increase in MMP-9 expression was found in breast cancer cells where compared to normal breast tissue. A positive correlation could also be established between elevated levels of MMP-9 and breast cancer of high histological grade. Furthermore, our results indicate that not only MMP-9 is differentially expressed between each molecular subset but also, more importantly MMP-9 overexpression revealed itself as a startling feature of triple-negative and HER2-positive breast cancers. Lastly, the clinical relevance of MMP-9 overexpression is strongly supported by its significant association with a higher incidence of metastasis and relapse.ConclusionsDifferential expression of MMP-9 reflects the extent of cellular differentiation in breast cancer cells and is closely related to the most aggressive subtypes of breast cancer. Hence, MMP-9 is a promising prognostic biomarker of high-grade breast cancer. In our opinion, MMP-9 expression could help segregate subsets of aggressive breast cancer into clinically meaningful subtypes.

Dataset Information

HERG1 channel expression associates with molecular subtypes and prognosis in breast cancer.

Publications

hERG1 channel expression associates with molecular subtypes and prognosis in breast cancer.

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