OCT4, SOX2, and NANOG positive expression correlates with poor differentiation, advanced disease stages, and worse overall survival in HER2+ breast cancer patients

Abstract

Objective: This study aimed to evaluate the correlations of expression of OCT4, SOX2, and NANOG with clinicopathological features and overall survival (OS) in human epidermal growth factor receptor 2-positive (HER2⁺) breast cancer (BC) patients.

Methods: One hundred and thirty-four surgical HER2⁺ BC patients who received doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab adjuvant therapy were enrolled in this study. Immunofluorescence assay was used to detect OCT4, SOX2, and NANOG expressions. The median follow-up duration was 104 months, and the last follow-up date was December 31, 2017.

Results: The expressions of OCT4 (P=0.001), SOX2 (P=0.003), and NANOG (P=0.005) were higher in tumor tissues compared with paired adjacent tissues. OCT4 positive expression was associated with poor pathological differentiation (P=0.028), larger tumor size (P=0.022), advanced N stage (P<0.001), and higher TNM stage (P<0.001). SOX2 positive expression was correlated with poor pathological differentiation (P=0.005), larger tumor size (P=0.013), and increased T stage (P=0.024). NANOG positive expression was associated with poor pathological differentiation (P=0.028), higher N stage (P=0.001), and elevated TNM stage (P=0.001). Kaplan-Meier curves disclosed that OCT4 (P=0.001) and NANOG (P=0.001) positive expressions were associated with worse OS, while SOX2 (P=0.058) positive expression was only numerically correlated with poor OS, but without statistical significance. Further analyses revealed that co-expression of these three biomarkers disclosed even better predictive value for shorter OS.

Conclusion: OCT4, SOX2, and NANOG positive expressions correlate with poor differentiation and advanced disease stage, and OCT4 and NANOG present with predictive values for poor OS in HER2⁺ BC patients.

Keywords: biomarker; clinicopathological features; predictive value; prognosis; tumor tissue.

Figure 1

OCT4, SOX2, and NANOG expressions in tumor tissues and paired adjacent normal tissues. Notes: The expressions of (A) OCT4, (B) SOX2, and (C) NANOG were higher in tumor tissues compared to adjacent tissues (original magnification: ×50). P<0.05 was considered significant.

Figure 2

The correlations of OCT4, SOX2, and NANOG expressions with OS in HER2⁺ BC patients. Notes: (A) Correlations of OCT4 positive expression and OCT4 negative expression with OS. (B) Correlations of SOX2 positive expression and SOX2 negative expression with OS. (C) Correlations of NANOG positive expression and NANOG negative expression with OS. Kaplan–Meier curves were used to analyze the correlations of OCT4, SOX2, and NANOG expressions with OS. Comparison of two groups was performed using log-rank test. P<0.05 was considered significant. Abbreviations: OS, overall survival; HER2, human epidermal growth factor receptor 2; BC, breast cancer.

Figure 3

The correlations of numbers of positive markers with OS in HER2⁺ BC patients. Notes: (A) Associations between OS and patients with no positive marker and patients with at least one positive marker. (B) Associations between OS and patients with one or no positive marker and patients with at least two positive markers. (C) Associations between OS and patients with two or less positive markers and patients with three positive markers. Kaplan–Meier curves were used to evaluate the correlation of number of positive markers with OS. Comparison of two groups was performed using log-rank test. P<0.05 was considered significant. Abbreviations: OS, overall survival; HER2, human epidermal growth factor receptor 2; BC, breast cancer.