HPD overexpression predicts poor prognosis in breast cancer

Xuanyu Wang; Yongjun Shang; Lina Yang; Xiaoyu Tan; Huamin Zhang; Changliang Shan; Shuangping Liu

doi:10.1016/j.prp.2019.152524

HPD overexpression predicts poor prognosis in breast cancer

Pathol Res Pract. 2019 Sep;215(9):152524. doi: 10.1016/j.prp.2019.152524. Epub 2019 Jun 28.

Authors

Xuanyu Wang¹, Yongjun Shang², Lina Yang¹, Xiaoyu Tan¹, Huamin Zhang³, Changliang Shan⁴, Shuangping Liu⁵

Affiliations

¹ Department of Pathology, Medical College, Dalian University, Dalian 116622, Liaoning, China.
² Department of Orthopedics, Xinhua Hospital Affiliated of Dalian University, Dalian 11602, Liaoning, China.
³ Department of Radiotherapy, The Second Hospital of Jilin University, Changchun 130022, Jilin, China.
⁴ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China; The First Affiliated Hospital, Biomedical Translational Research Institute, Jinan University, Guangzhou 510632, Guangdong, China. Electronic address: changliangshan@nankai.edu.cn.
⁵ Department of Pathology, Medical College, Dalian University, Dalian 116622, Liaoning, China. Electronic address: liushuangping@dlu.edu.cn.

PMID: 31277952
DOI: 10.1016/j.prp.2019.152524

Abstract

Background: The enzyme, 4-hydroxyphenylpyruvate dioxygenase (HPD), is critical to tyrosine metabolism; its deficiency can cause tyrosinemia. However, its precise contribution to tumorigenesis is unclear. Here, we investigated the correlation between HPD expression and prognosis in patients with breast cancer.

Methods: 145 breast cancer specimens were selected to analyze HPD protein expression by immunohistochemistry and evaluate its relationship to patients' clinicopathological features. HPD localization was confirmed in MCF-7 and MDA-MB-231 breast cancer cells, using immunofluorescence staining. The expression of HPD protein was detected in breast cancer and cancer-adjacent normal tissues using Western blot analysis. Survival rates were calculated by the Kaplan-Meier method.

Results: We found that HPD protein was mainly located in the cytoplasm/nucleoli/perinucleus in breast cancer cells, as shown by immunofluorescence staining in MCF-7 and MDA-MB-231 cells, and immunohistochemistry in breast cancer and adjacent normal tissues (HPD protein expression-breast cancer: 46.9% [68/145], ductal carcinoma in situ [DCIS]: 22.6% [12/53], and normal tissues: only 4.8% [2/42]). Similarly, the Western blot results further confirmed the increased expression of HPD in breast cancer compared with cancer-adjacent normal tissues (P < 0.05). HPD expression level was positively correlated with histological grade and clinical stage, and inversely correlated with 10-year overall survival (OS) rates, in patients with breast cancer. Among patients with breast cancer, those with high HPD expression had worse OS rates than those with low HPD expression. Additionally, when patients were subgrouped by disease stage or grade, those with high HPD expression had worse OS rates than those with low HPD expression for each respective stage or grade.

Conclusions: Our findings indicate that HPD may be a useful prognostic predictor, and a potential therapeutic target for patients with breast cancer.

Keywords: Breast cancer; HPD; Prognosis.

MeSH terms

4-Hydroxyphenylpyruvate Dioxygenase / analysis
4-Hydroxyphenylpyruvate Dioxygenase / biosynthesis*
Adult
Aged
Biomarkers, Tumor / analysis*
Breast Neoplasms / enzymology*
Breast Neoplasms / mortality
Breast Neoplasms / pathology
Female
Humans
Kaplan-Meier Estimate
Middle Aged
Prognosis
Up-Regulation

Substances

Biomarkers, Tumor
4-Hydroxyphenylpyruvate Dioxygenase