Characterization of glucose metabolism in breast cancer to guide clinical therapy

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 (...

Full description

Bibliographic Details
Main Authors: Yingying Mei, Lantao Zhao, Man Jiang, Fangfang Yang, Xiaochun Zhang, Yizhen Jia, Na Zhou
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Surgery
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fsurg.2022.973410/full
_version_ 1797997338110722048
author Yingying Mei
Lantao Zhao
Man Jiang
Fangfang Yang
Xiaochun Zhang
Yizhen Jia
Na Zhou
author_facet Yingying Mei
Lantao Zhao
Man Jiang
Fangfang Yang
Xiaochun Zhang
Yizhen Jia
Na Zhou
author_sort Yingying Mei
collection DOAJ
description 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.
first_indexed 2024-04-11T10:31:11Z
format Article
id doaj.art-4011ae574e1e4d3fafc6ffe506fcaeb8
institution Directory Open Access Journal
issn 2296-875X
language English
last_indexed 2024-04-11T10:31:11Z
publishDate 2022-09-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Surgery
spelling doaj.art-4011ae574e1e4d3fafc6ffe506fcaeb82022-12-22T04:29:25ZengFrontiers Media S.A.Frontiers in Surgery2296-875X2022-09-01910.3389/fsurg.2022.973410973410Characterization of glucose metabolism in breast cancer to guide clinical therapyYingying Mei0Lantao Zhao1Man Jiang2Fangfang Yang3Xiaochun Zhang4Yizhen Jia5Na Zhou6Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, ChinaDepartment of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaPrecision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, ChinaPrecision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, ChinaPrecision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, ChinaCore Laboratory, The University of Hong Kong-Shenzhen Hospital, Shenzhen, ChinaPrecision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, ChinaBackgroundBreast 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.https://www.frontiersin.org/articles/10.3389/fsurg.2022.973410/fullbreast cancerglucose metabolismprognosisimmune infiltrationdrug sensitivity
spellingShingle Yingying Mei
Lantao Zhao
Man Jiang
Fangfang Yang
Xiaochun Zhang
Yizhen Jia
Na Zhou
Characterization of glucose metabolism in breast cancer to guide clinical therapy
Frontiers in Surgery
breast cancer
glucose metabolism
prognosis
immune infiltration
drug sensitivity
title Characterization of glucose metabolism in breast cancer to guide clinical therapy
title_full Characterization of glucose metabolism in breast cancer to guide clinical therapy
title_fullStr Characterization of glucose metabolism in breast cancer to guide clinical therapy
title_full_unstemmed Characterization of glucose metabolism in breast cancer to guide clinical therapy
title_short Characterization of glucose metabolism in breast cancer to guide clinical therapy
title_sort characterization of glucose metabolism in breast cancer to guide clinical therapy
topic breast cancer
glucose metabolism
prognosis
immune infiltration
drug sensitivity
url https://www.frontiersin.org/articles/10.3389/fsurg.2022.973410/full
work_keys_str_mv AT yingyingmei characterizationofglucosemetabolisminbreastcancertoguideclinicaltherapy
AT lantaozhao characterizationofglucosemetabolisminbreastcancertoguideclinicaltherapy
AT manjiang characterizationofglucosemetabolisminbreastcancertoguideclinicaltherapy
AT fangfangyang characterizationofglucosemetabolisminbreastcancertoguideclinicaltherapy
AT xiaochunzhang characterizationofglucosemetabolisminbreastcancertoguideclinicaltherapy
AT yizhenjia characterizationofglucosemetabolisminbreastcancertoguideclinicaltherapy
AT nazhou characterizationofglucosemetabolisminbreastcancertoguideclinicaltherapy