A Novel Prognostic Biomarker of Luminal Breast Cancer: High CD39 Expression Is Related to Poor Survival.

Xiaojian Ni,Wenze Wan,Lihong Huang,Jingjing Ma,Xinyou Liu,Weige Yang,Bohao Zheng,Zhixian He

doi:10.3389/fgene.2021.682503

Abstract

BackgroundCD39 is one of the functional surface markers for T regulatory cells, the prognostic role and immune-related effects of CD39 in luminal breast cancer (BC) patients has not been evaluated yet. The aim of the current study was to explore the association between CD39 expression and clinic pathological characteristics and the prognosis in luminal BC patients.MethodsClinical information and RNA-sequencing (RNA-Seq) expression data were extracted from The Cancer Genome Atlas (TCGA). Patients were divided into a high or low CD39 expression group by the optimal cutoff value (4.18) identified from the receiver operating characteristic curve analysis. The relationships between CD39 expression and clinic pathological features were evaluated by the corresponding statistical tests. Survival analyses were applied to evaluate the overall survival between the high and low CD39 expression groups in luminal BC. Furthermore, Gene Expression Omnibus datasets were used for external data validation. Gene set enrichment analysis (GSEA) was also performed, and CIBERSORT was used to analyze the immune cell populations.ResultsAnalysis of 439 cases of tumor data showed that CD39 was overexpressed in luminal BC. The multivariable analysis suggested that CD39 expression was an independent prognostic factor for luminal BC patients. GSEA suggested that CD39 might play an important role in luminal BC progression through immune regulation. Analysis of immune cell patterns revealed high CD39 expression correlated to a higher proportion of CD8+ T cells and M2 macrophages.ConclusionThis study demonstrates that CD39 expression correlates with the prognosis of luminal BC through TCGA database mining. Further studies are warranted further to elucidate this potential novel therapeutic strategy for BC.

Highlights

Breast cancer (BC) is the most familiar malignant neoplasm in women worldwide, with multiple molecular subtypes (Siegel and Miller, 2020)
In the investigated population (N = 439), most luminal BC patients were not Hispanic or Latino (74.72%), and nearly half of the BC patients were older than 60 years (47.61%)
In terms of BC subtypes, 66.51% of the 439 luminal BC patients were classified as infiltrating ductal carcinoma, and 23.01% were infiltrating lobular carcinoma

Summary

Introduction

Breast cancer (BC) is the most familiar malignant neoplasm in women worldwide, with multiple molecular subtypes (Siegel and Miller, 2020). Luminal A-like tumors were defined as estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 negatives (HER2−), progesterone receptor (PR) ≥ 20%, Ki67 < 14% which has “low” recurrence risk assessed by gene assays (Goldhirsch et al, 2013). Luminal B-like tumors were defined as ER+, HER2−, and at least one of the following: PR negative < 20%, Ki67 ≥ 20%, and which has “high” recurrence risk based on gene assays. BC has a better prognosis and a higher overall survival (OS) rate, especially the luminal subtypes (Kennecke et al, 2010; Wu et al, 2017), it remains a challenge to reduce BC’s bone metastasis and mortality. Identifying novel molecular signature to predict BC’s prognosis, especially the most common luminal ERα+ subtype, is of great importance. The aim of the current study was to explore the association between CD39 expression and clinic pathological characteristics and the prognosis in luminal BC patients

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