Prognostic model of invasive ductal carcinoma of the breast based on differentially expressed glycolysis-related genes

PeerJ. 2020 Nov 4;8:e10249. doi: 10.7717/peerj.10249. eCollection 2020.

Abstract

Background: Invasive ductal carcinoma (IDC) is a common pathological type of breast cancer that is characterized by high malignancy and rapid progression. Upregulation of glycolysis is a hallmark of tumor growth, and correlates with the progression of breast cancer. We aimed to establish a model to predict the prognosis of patients with breast IDC based on differentially expressed glycolysis-related genes (DEGRGs).

Methods: Transcriptome data and clinical data of patients with breast IDC were from The Cancer Genome Atlas (TCGA). Glycolysis-related gene sets and pathways were from the Molecular Signatures Database (MSigDB). DEGRGs were identified by comparison of tumor tissues and adjacent normal tissues. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to screen for DEGRGs with prognostic value. A risk-scoring model based on DEGRGs related to prognosis was constructed. Receiver operating characteristic (ROC) analysis and calculation of the area under the curve (AUC) were used to evaluate the performance of the model. The model was verified in different clinical subgroups using an external dataset (GSE131769). A nomogram that included clinical indicators and risk scores was established. Gene function enrichment analysis was performed, and a protein-protein interaction network was developed.

Results: We analyzed data from 772 tumors and 88 adjacent normal tissues from the TCGA database and identified 286 glycolysis-related genes from the MSigDB. There were 185 DEGRGs. Univariate Cox regression and LASSO regression indicated that 13 of these genes were related to prognosis. A risk-scoring model based on these 13 DEGRGs allowed classification of patients as high-risk or low-risk according to median score. The duration of overall survival (OS) was longer in the low-risk group (P < 0.001), and the AUC was 0.755 for 3-year OS and 0.726 for 5-year OS. The results were similar when using the GEO data set for external validation (AUC for 3-year OS: 0.731, AUC for 5-year OS: 0.728). Subgroup analysis showed there were significant differences in OS among high-risk and low-risk patients in different subgroups (T1-2, T3-4, N0, N1-3, M0, TNBC, non-TNBC; all P < 0.01). The C-index was 0.824, and the AUC was 0.842 for 3-year OS and 0.808 for 5-year OS from the nomogram. Functional enrichment analysis demonstrated the DEGRGs were mainly involved in regulating biological functions.

Conclusions: Our prognostic model, based on 13 DEGRGs, had excellent performance in predicting the survival of patients with IDC of the breast. These DEGRGs appear to have important biological functions in the progression of this cancer.

Keywords: Breast invasive ductal carcinoma; Function enrichment analysis; Glycolysis; Nomogram.

Grant support

This work was supported by the Guangdong Medical Research Foundation (Grant No. A2020622) and the Elite Young Scholars Program of Jiangmen Central Hospital (Grant No. J201905). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.