Characterization of glucose metabolism in breast cancer to guide clinical therapy

Abstract

BackgroundBreast cancer (BRCA) ranks as a leading cause of cancer death in women worldwide. Glucose metabolism is a noticeable characteristic of the occurrence of malignant tumors. In this study, we aimed to construct a novel glycometabolism-related gene (GRG) signature to predict overall survival (OS), immune infiltration and therapeutic response in BRCA patients.Materials and methodsThe mRNA sequencing and corresponding clinical data of BRCA patients were obtained from public cohorts. Lasso regression was applied to establish a GRG signature. The immune infiltration was evaluated with the ESTIMATE and CIBERSORT algorithms. The drug sensitivity was estimated using the value of IC50, and further forecasted the therapeutic response of each patient. The candidate target was selected in Cytoscape. A nomogram was constructed via the R package of “rms”.ResultsWe constructed a six-GRG signature based on CACNA1H, CHPF, IRS2, NT5E, SDC1 and ATP6AP1, and the high-risk patients were correlated with poorer OS (P = 2.515 × 10−7). M2 macrophage infiltration was considerably superior in high-risk patients, and CD8+ T cell infiltration was significantly higher in low-risk patients. Additionally, the high-risk group was more sensitive to Lapatinib. Fortunately, SDC1 was recognized as candidate target and patients had a better OS in the low-SDC1 group. A nomogram integrating the GRG signature was developed, and calibration curves were consistent between the actual and predicted OS.ConclusionsWe identified a novel GRG signature complementing the present understanding of the targeted therapy and immune biomarker in breast cancer. The GRGs may provide fresh insights for individualized management of BRCA patients.

SDC1 and ITGA2 as novel prognostic biomarkers for PDAC related to IPMN

“…SDC1 high has varying significance in different kinds of cancer. SDC1 high might predict a poor prognosis of breast cancer, but a better prognosis of colorectal cancer 28 , 29 . To date, few studies have investigated the role of SDC1 in PC 30 .…”

Clinicopathologic features and genomic profiling of female axillary lymph node metastases from adenocarcinoma or poorly differentiated carcinoma of unknown primary

“…But the drug sensitivity of IRS2 amplification in breast cancer remains unclear. A recent study established a sugar metabolism-related prognostic model that included IRS2 gene for breast cancer, which could distinguish low-risk patients who were more sensitive to chemotherapy (Mei et al 2022 ). In our study, CUPAx patients with IRS2 mutations showed higher pCR rates (3/4) to neoadjuvant chemotherapy than BCAx patients (0/2) (75% vs. 0%).…”

Bibliometric analysis of phosphoglycerate kinase 1 expression in breast cancer and its distinct upregulation in triple-negative breast cancer

“…Under aerobic conditions, normal cells obtain energy by oxidative phosphorylation (OXPHOS) in the mitochondria. In hypoxia, cells acquire energy via the metabolic pathway of glycolysis rather than mitochondrial processes that consume oxygen[ 54 ]. Despite the availability of sufficient oxygen, malignant tumor cells continue to fulfill their metabolic demands through the glycolytic mode rather than OXPHOS, and this phenomenon is referred to aerobic glycolysis or the Warburg effect[ 55 , 56 ].…”