Ectopic expression of HSDL2 is related to cell proliferation and prognosis in breast cancer

Abstract

Purpose: Human hydroxysteroid dehydrogenase-like 2 (HSDL2) is a characterized SDR gene that not only catalyses the oxidation and reduction of multiple substrates but also regulates different metabolic and signalling pathways. Accumulating evidences suggest that HSDL2 play an important role in cancer progression. However, the role of HSDL2 in breast cancer has not yet been determined. Thus, this study aims to explore the relevance of HSDL2 in breast cancer progression. Patients and methods: The location of HSDL2 protein was detected in MDA-MB-231 breast cancer cells by using immunofluorescence (IF) staining. The expression level of HSDL2 was evaluated by immunohistochemical (IHC) staining in 119 breast cancer tissues and 40 normal breast tissues. Then, the correlations between the overexpression of HSDL2 and clinicopathological features of breast cancer patients were evaluated by using the chi-square test, and the survival rates were calculated by the Kaplan-Meier method. In addition, the role of HSDL2 in breast cancer proliferation was assessed by MTT and colony formation assays, and cell cycle distribution was detected by flow cytometry analysis and Western blot. Results: IF staining and IHC analysis consistently showed that HSDL2 was predominantly expressed in the cytoplasm of breast cancer cells. The positive rate of HSDL2 protein was significantly higher in breast cancer tissues (87.4%, 104/119) than in adjacent normal breast tissues (25%, 10/40) (p<0.01). A high expression of HSDL2 protein was significantly associated with high histological grades, late clinical stages and low survival rates. Moreover, multivariate analysis indicated that HSDL2 protein was an independent prognostic factor in breast cancer patients. Studies in vitro showed that HSDL2 depletion reduced cell proliferation and induced cell cycle arrest in breast cancer. Conclusion: In conclusion, this study indicated that HSDL2 plays a role in promoting the development of breast cancer. HSDL2 could be a valuable prognostic biomarker and a potential therapeutic target for patients with breast cancer.