Serum Soluble CD14 Is a Potential Prognostic Indicator of Recurrence of Human Breast Invasive Ductal Carcinoma with Her2-Enriched Subtype

Weifeng He,Gaoxing Luo,Jingjing Liu,Yifan Tong,Jun Wu,Jin Zhang,Ying Wang,Xin-Yuan Guan

doi:10.1371/journal.pone.0075366

Abstract

In clinical practice, breast cancers with lymph node positive, ER/PR-negative and overexpressed human epidermal growth factor receptor 2 (LN+ER/PR-Her2+) have high risk of recurrence, but the effective biomarkers of prognostic for this type tumor are still lacking. Since breast cancers with LN+ER/PR-Her2+ is at higher risk of recurrence than those with LN-ER/PR+Her2-. The differential proteins between those two groups could be related to the risk of recurrence. Herein, we report that serum soluble CD14 (sCD14) was revealed as the stable differential protein between LN+ER/PR-Her2+ (n=50) and LN-ER/PR+Her2- (n=50) breast cancer patients by proteomics analysis. To validate sCD14 as a biomarker for predicting recurrence of breast cancer, 90 breast cancer patients with LN+ER/PR-Her2+ and 93 patients with LN-ER/PR+Her2- were recruited. The patients with higher level of serum sCD14 at primary surgery showed to be at significantly lower risk of relapse in 3 years follow-up than those with lower level of serum sCD14 at primary surgery. The levels of serum sCD14 at primary surgery were significantly correlated to the risk of 3-year recurrence of LN+ER/PR-Her2+ breast cancer and the corresponding AUC of the ROC curve was 0.833 (95% CI, and 0.742 to 0.920). Therefore, we surmise that serum sCD14 could be a potential biomarker for predicting the prognosis of breast invasive ductal carcinoma with LN+ER/PR-Her2+.

Highlights

Breast cancer is the leading cause of cancer death in females worldwide [1] and the identification of its prognostic biomarkers could be valuable for improving the clinical management
Serum soluble CD14 (sCD14) was significantly different between LNER/progesterone receptor (PR)+human epidermal growth factor receptor 2 (Her2)- and LN+estrogen receptor (ER)/PR-Her2+ status breast cancer groups
To analyze serum differential proteins between patients with LN-ER/PR+Her2status and LN+ER/PR-Her2+ status, we arbitrarily set the criterion of differential protein as spectra counts ratio of LNER/PR+Her2- and LN+ER/PR-Her2+ datasets ≥10 or ≤0.1

Summary

Introduction

Breast cancer is the leading cause of cancer death in females worldwide [1] and the identification of its prognostic biomarkers could be valuable for improving the clinical management. Breast cancer with overexpressed human epidermal growth factor receptor 2 (Her2) is characterized by aggressive progress and shortened survival [2,3]. The effective prognostic biomarkers for the two types of breast cancers are still lacking. It’s reasonable to assume that the differential serum proteins between those two groups might be correlated to the risk of breast cancer relapse. We comparatively studied the serum protein profile of breast invasive ductal carcinoma with a lower risk of recurrence (LN-ER/PR+Her2-; n=50) and those with a higher risk of recurrence (LN+ER/PR-Her2+; n=50) by proteomics, and proposed that serum sCD14 is a potential biomarker for predicting recurrence of LN+ER/PR-Her2+ status breast cancer

Methods

Results

Discussion

Conclusion