Identifying Biomarkers to Predict the Progression and Prognosis of Breast Cancer by Weighted Gene Co-expression Network Analysis.

Gengsheng Shi,Wenqin Yin,Zhenru Shen,Yi Liu

doi:10.3389/fgene.2020.597888

Abstract

Breast cancer (BC) is the leading cause of cancer death among women worldwide. The molecular mechanisms of its pathogenesis are still to be investigated. In our study, differentially expressed genes (DEGs) were screened between BC and normal tissues. Based on the DEGs, a weighted gene co-expression network analysis (WGCNA) was performed in 683 BC samples, and eight co-expressed gene modules were identified. In addition, by relating the eight co-expressed modules to clinical information, we found the blue module and pathological stage had a significant correlation (r = 0.24, p = 1e–10). Validated by multiple independent datasets, using one-way ANOVA, survival analysis and expression level revalidation, we finally screened 12 hub genes that can predict BC progression and prognosis. Functional annotation analysis indicated that the hub genes were enriched in cell division and cell cycle regulation. Importantly, higher expression of the 12 hub genes indicated poor overall survival, recurrence-free survival, and disease-free survival in BC patients. In addition, the expression of the 12 hub genes showed a significantly positive correlation with the expression of cell proliferation marker Ki-67 in BC. In summary, our study has identified 12 hub genes associated with the progression and prognosis of BC; these hub genes might lead to poor outcomes by regulating the cell division and cell cycle. These hub genes may serve as a biomarker and help to distinguish different pathological stages for BC patients.

Highlights

In 2018, there are approximately 2.1 million new cases of breast cancer (BC) and 630,000 deaths worldwide (Bray et al, 2018)
weighted gene co-expression network analysis (WGCNA) has been used to identify biomarkers related to Breast cancer (BC) progression in recent publications
By 2019, about 268,600 invasive BC and 48,100 DCIS cases were diagnosed among American women, and 41,760 women will die of the disease

Summary

Introduction

In 2018, there are approximately 2.1 million new cases of breast cancer (BC) and 630,000 deaths worldwide (Bray et al, 2018). Adjuvant therapies have reduced BC-related mortality, up to 25% of patients will develop tumor relapse (Early Breast Cancer Trialists’ Collaborative Group et al, 2012; Howlader et al, 2014). The mortality of BC is largely due to recurrent tumors (Berry et al, 2005). BC patients with higher clinical stage are more likely to recurrence and have worse prognosis (Garcia-Murillas et al, 2015). Genetic mutations have a key role in the progression of BC. BRAF mutations were present in over 3% of metastatic BC patients (Cejalvo et al, 2016). There have been great advances in the treatment of BC, the ability to treat advanced BC is still

Methods

Results

Conclusion