Zhang D, Wang M, Huang X, Wang L, Liu Y, Zhou S, Tang Y, Wang Q, Li Z, Wang G. GLS as a diagnostic biomarker in breast cancer: in-silico, in-situ, and in-vitro insights.
Front Oncol 2023;
13:1220038. [PMID:
37664031 PMCID:
PMC10471892 DOI:
10.3389/fonc.2023.1220038]
[Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 07/31/2023] [Indexed: 09/05/2023] Open
Abstract
Background
Recently, 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 methods
Bulk 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.
Results
Pan-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.
Conclusion
We 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.
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