GLS as a diagnostic biomarker in breast cancer: in-silico, in-situ, and in-vitro insights

Frontiers in Oncology

Oncology

Ying Liu¹  Danfeng Zhang²  Geng Wang²  Man Wang³  Zhengrui Li⁴  Xufeng Huang⁵  Longbin Wang⁶  Qi Wang⁷  Shujing Zhou⁸  Yidan Tang⁸ 

[1] Department of Cardiology, Sixth Medical Center, PLA General Hospital, Beijing, China;Departments of Breast Thyroid Vascular Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China;Departments of Outpatient Department, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China;Faculty of Dentistry, Shanghai Jiaotong University, Shanghai, China;Faculty of Dentistry, University of Debrecen, Debrecen, Hungary;Faculty of Life Science, Huazhong Agricultural University, Wuhan, China;Faculty of Medicine, Jiangsu University, Zhenjiang, China;Faculty of Medicine, University of Debrecen, Debrecen, Hungary;

关键词: breast cancer;    bioinformatics;    cuproptosis;    biomarker;    EMT pathway;   

DOI  :  10.3389/fonc.2023.1220038

 received in 2023-05-12, accepted in 2023-07-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundRecently, a novel programmed cell death mechanism, Cuproptosis, has been discovered and found to play an important role in the development and progression of diverse tumors. In the present study, we comprehensively investigated the core gene of this mechanism, GLS, in breast cancer.Materials and methodsBulk RNA sequencing data were curated from the TCGA repository to investigate the aberrant expression of GLS over diverse cancer types. Then, we examined its efficacy as a diagnostic biomarker in breast cancer by Area Under Curve (AUC) of the Receiver Operative Characteristic (ROC) curve. Furthermore, by applying siRNA technique, we knocked down the GLS expression level in cancerous cell lines, measuring the corresponding effects on cell proliferation and metastasis. Afterward, we explored the potential implications of GLS expression in the tumor immune microenvironment quantitatively by using several R packages and algorithms, including ESTIMATE, CIBERSORT, etc.ResultsPan-cancer analysis suggested that GLS was aberrantly over-expressed in many cancer types, with breast cancer being typical. More in-depth analyses revealed the expression of GLS exerted a high ROC-AUC value in breast cancer diagnosis. Through the knock-down of GLS expression, it was found that GLS expression was strongly relevant to the growth and metastasis of tumor. Furthermore, it was also found to be correlated with the immune tumor microenvironment.ConclusionWe highlighted that GLS expression might be applicable as a diagnostic biomarker in breast cancer and possess significant implications in the growth and metastasis of tumor and the immune tumor microenvironment, sharing new insights into ontological and personalized medicine.

【 授权许可】

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Copyright © 2023 Zhang, Wang, Huang, Wang, Liu, Zhou, Tang, Wang, Li and Wang