GOLPH3: a novel biomarker that correlates with poor survival and resistance to chemotherapy in breast cancer.

Shicong Tang,Hong Pan,Jianlun Liu,Wei Wei,Rirong Yang,Huawei Yang

doi:10.18632/oncotarget.21927

Abstract

The association between Golgi phosphoprotein 3 (GOLPH3) and clinical pathological characteristics, as well as the clinical outcomes of both neoadjuvant and adjuvant chemotherapies in breast cancer, remain largely unknown. In this study, we investigated the biological role and clinical significance of GOLPH3 in breast cancer. We found that GOLPH3 expression in tumor tissue was higher than that in adjacent noncancerous tissue (ANT) and fibroadenoma. GOLPH3 silencing reduced the migration, invasion, and proliferation of breast cancer cells and promoted apoptosis of the cells. Importantly, patients with high GOLPH3 expression had worse disease-free survival (DFS) and overall survival (OS), and GOLPH3 expression was correlated with clinical pathological characteristics such as molecular subtype, tumor-node-metastasis classification, and age but was not associated with surgery type. Patients with high GOLPH3 expression had poor DFS and OS in every molecular subtype, and an increase in tumor invasion and lymph node metastasis. The risk of recurrence increased with age in patients with high GOLPH3 expression, and surgery type had no influence on patient survival. This is the first study to investigate the correlation between GOLPH3 and response to chemotherapy in breast cancer. Patients with high GOLPH3 expression showed resistance to neoadjuvant and adjuvant chemotherapies, and GOLPH3 overexpression indicated a high risk of recurrence in patients who received adjuvant chemotherapy. These data suggest that GOLPH3 may be a novel biomarker that correlates with poor survival and resistance to chemotherapy in breast cancer.

Highlights

Breast cancer is the most common malignant tumor in females worldwide [1,2,3], and its incidence is increasing [4]
Golgi phosphoprotein 3 (GOLPH3) was found to be highly expressed in breast cancer tissue and cell lines
Patients with GOLPH3 overexpression had poor disease-free survival (DFS) and overall survival (OS), and GOLPH3 expression was associated with clinicopathologic factors such as age, TNM classification, and molecular subtype but did www.impactjournals.com/oncotarget

Summary

Introduction

Breast cancer is the most common malignant tumor in females worldwide [1,2,3], and its incidence is increasing [4]. GOLPH3 is a highly conserved 34-kDa trans-Golgi matrix membrane protein that plays a key role in receptor recycling, glycosylation, and protein trafficking from Golgi to the plasma membrane [8,9,10,11]. It is suggested that GOLPH3 functions as an oncogene in tumorigenesis and migration [12,13,14,15] by activating the mechanistic target of rapamycin www.impactjournals.com/oncotarget (mTOR), Wnt, and nuclear factor kappa-light-chainenhancer of activated B cells (NF-kB) signaling pathways and by upregulating matrix metalloproteinases (MMPs) such as MMP-2 and MMP-9 [16,17,18,19]. Zeng et al [26] found that GOLPH3 is highly expressed in breast cancer, but its function needs further investigation

Methods

Results

Conclusion