Association of Enolase-1 with Prognosis and Immune Infiltration in Breast Cancer by Clinical Stage

Abstract

Purpose

Enolase-1 (ENO1) plays a key role in malignancies. Previous studies on the association between ENO1 expression and breast cancer prognosis had yielded inconsistent results. In the present study, we assessed the prognostic effect of ENO1 in breast cancer using Guangzhou Breast Cancer Study (GZBCS) cohort with full consideration of the potential confounders and the modification effects. The results were further validated in the TCGA-BRCA cohort and explained by tumor immunity.

Methods

ENO1 protein expressions were evaluated by immunohistochemistry in tissue microarrays from 961 patients with primary invasive breast cancer. Chi-square tests were used to assess the association of ENO1 levels with the patient’s characteristics. Cox regression models were applied to assess the prognostic effects. The TCGA-BRCA cohort was utilized to validate the results and explore the potential mechanisms. The immune infiltration was determined using the CIBERSORT and ssGSEA algorithms; the correlation between ENO1 expression and the abundance of tumor-infiltrating immune cells (TIICs) and scores of immune-related functions was evaluated by Wilcoxon signed-rank tests and Spearman’s rank test.

Results

ENO1 protein expression exerted a protective effect on OS in stage I/II patients (HR=0.58, 95% CI: 0.35–0.96) but not in stage III patients (HR=1.42, 95% CI: 0.81–2.49, P _interaction=0.04) in GZBCS; consistent results were obtained at mRNA levels in TCGA cohort. Immune infiltration analyses revealed that ENO1 was positively correlated with multiple antitumor TIICs (including M1 macrophages, B cells, CD8 T cells, T helper 2 cells, and NK cells) only in stage I/II but not stage III patients.

Conclusion

A higher expression of ENO1 was associated with a better prognosis only in early-stage breast cancer, which may be related to the different effects of ENO1 on immune infiltration, suggesting that ENO1 may be a promising target for precision immunotherapy in breast cancer.

Keywords:

• ENO1
• breast cancer
• prognosis
• tissue microarray
• tumor-infiltrating immune cells

Data Sharing Statement

The public datasets analyzed during the present study are available from TCGA (https://portal.gdc.cancer.gov/) data portal. The IHC data generated during and analyzed during the current study are available from the corresponding author on reasonable request.

Ethical Statement

The public datasets analyzed during the present study are available from TCGA (https://portal.gdc.cancer.gov/) data portal, which allowed researchers to download and analyze datasets for scientific purposes free of charge and without ethical issues. The protocol of the GZBCS cohort was approved by the Ethics Committee of School of Public Health, Sun Yat-sen University. All participants provided written informed consent.

Acknowledgments

We sincerely thank the patients who participated in this study, the staff who conducted the baseline and the follow-up data collection, and the medical staff in the breast departments of the First Affiliated Hospital, and the Cancer Center of Sun Yat-sen University.

Disclosure

The authors declare no conflicts of interest in this work.

Additional information

Funding

This research was supported by the National Natural Science Foundation of China (81973115) and Science and Technology Planning Project of Guangdong Province, China (2019B030316002). The founders have no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.