Abstract

ObjectiveThe study aimed to compare the Steroid 5 alpha-reductase 3 (SRD5A3) expression levels in breast cancer (BC) and normal tissues, to investigate the prognostic value of SRD5A3 mRNA expression in BC patients and to identify the SRD5A3-related signaling pathways using bioinformatics approaches.MethodsWe evaluated the expression levels of SRD5A3 and survival data in BC patients using different bioinformatic databases. Further, Cox regression analysis was conducted to predict the independent prognostic factors for BC. Moreover, the association of SRD5A3 with clinicopathological factors was measured through LinkedOmics database. And the potential role of SRD5A3 was determined by Gene Ontology and KEGG pathway enrichment analysis. Finally, protein network of SRD5A3 was constructed and genetic alterations were analyzed.ResultsBioinformatic data indicated that both mRNA and protein expression levels of SRD5A3 were higher in BC group than those in the normal group (P < 0.05). Besides, BC patients with higher SRD5A3 mRNA expression levels had a lower overall survival (all P < 0.05). Cox regression analysis further demonstrated the independent prognostic value of SRD5A3 in BC (P = 0.015). SRD5A3 mRNA expression was significantly associated with N stage (P < 0.001), age (P < 0.05), and histologic subtype (P < 0.001) but had no significant relationship with other clinical characteristics (all P > 0.05). Moreover, the functional enrichment analysis revealed that the SRD5A3 was involved in metabolism-related pathways (all P < 0.05).ConclusionsSRD5A3 was highly expressed in BC tissues and high SRD5A3 expression was related to poorer prognosis. SRD5A3 serves as an oncogene and might function as a potential biomarker for prognosis and a therapeutic target for BC.

Highlights

  • Breast cancer (BC) is one of the most common malignancies among women, accounting for 20% of all cancers and 22% of deaths [1]

  • The results showed that Steroid 5 alpha-reductase 3 (SRD5A3) protein is expressed in the plasma membrane and cytosol, while no SRD5A3 expression is detected in the nucleus (Fig. 1A)

  • SRD5A3 over-expression in BC To investigate the expression of SRD5A3 in BC, we first visualized the mRNA expression of SRD5A3 in human cancer and normal specimens using the Oncomine database

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Summary

Introduction

Breast cancer (BC) is one of the most common malignancies among women, accounting for 20% of all cancers and 22% of deaths [1]. It is classified into three subtypes: triple-negative breast cancer (TNBC), human epidermal growth factor receptor 2-positive (HER2+) BC, and estrogen receptor-positive (ER+)/luminal BC [2]. In the USA, one in eight women is diagnosed with BC, resulting in more than 252,710 new cases of this disease each year [3]. The improvement of the BC treatment has been achieved in the last decade, including radiation, chemotherapy and endocrine therapies, and targeted therapies.

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