CX3CL1 promotes cell sensitivity to ferroptosis and is associated with the tumor microenvironment in clear cell renal cell carcinoma

Background An increasing number of studies have demonstrated that CX3CL1 is involved in the development of tumors and may thus be considered a new potential therapeutic target for them. However, the function of CX3CL1 in clear cell renal cell carcinoma (ccRCC) remains poorly defined. Methods The pan...

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Bibliographic Details
Published in:BMC cancer 2022-11, Vol.22 (1), p.1-1184, Article 1184
Main Authors: Gong, Qiming, Guo, Zhiting, Sun, Wenjuan, Du, Xiuri, Jiang, Yan, Liu, Fahui
Format: Article
Language:English
Subjects:
Analysis
Antibodies
Apoptosis
cancer
Cancer and Oncology
Cancer och onkologi
Carcinoma, Renal cell
Care and treatment
CD8 antigen
Cell death
Cell proliferation
Cell viability
Chemokines
Clear cell renal cell carcinoma
Clear cell-type renal cell carcinoma
CX3CL1
Diagnosis
DNA methylation
Epigenetics
Experiments
Ferroptosis
fractalkine
Gene expression
Health aspects
high expression
immunity
Immunotherapy
Kidney cancer
Kinases
Lymphocytes T
Medical prognosis
Metastases
Molecular biology
Oncology
Patient outcomes
prognosis
Statistical analysis
Statistical significance
survival
Survival analysis
Therapeutic targets
Tumor cells
Tumor microenvironment
Tumor suppressor genes
Tumors
Xenografts
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Summary:Background An increasing number of studies have demonstrated that CX3CL1 is involved in the development of tumors and may thus be considered a new potential therapeutic target for them. However, the function of CX3CL1 in clear cell renal cell carcinoma (ccRCC) remains poorly defined. Methods The pan-cancer expression pattern and prognostic value of CX3CL1 were evaluated in this study. Moreover, the relationship of CX3CL1 expression with the tumor microenvironment, especially the tumor immune microenvironment, was analyzed. Our analyses employed public repository data. Additionally, we generated stable CX3CL1-overexpressing 786-O cells to determine the role of CX3CL1 in vitro via cell viability and transwell assays. A xenograft tumor model was used to determine the role of CX3CL1 in vivo. The association between CX3CL1 and ferroptosis sensitivity of tumor cells was assessed using Ferrostatin-1. Results Our findings indicated the involvement of CX3CL1 in the occurrence and development of ccRCC by acting as a tumor suppressor. We also found that ccRCC patients with high CX3CL1 expression showed better clinical outcomes than those with low CX3CL1 expression. The findings of our epigenetic study suggested that the expression of CX3CL1 in ccRCC is correlated with its DNA methylation level. Furthermore, the CX3CL1 expression level was closely related to the infiltration level of CD8.sup.+ T cells into the tumor microenvironment (TME). CX3CL1 showed different predictive values in different immunotherapy cohorts. Finally, CX3CL1 overexpression inhibited tumor cell proliferation and metastasis and promoted tumor ferroptosis sensitivity in ccRCC. Conclusions This study revealed the role of CX3CL1 as a tumor suppressor in ccRCC. Our findings indicated that CX3CL1 plays a crucial role in regulating the ccRCC TME and is a potential predictor of immunotherapy outcomes in ccRCC. We also found that CX3CL1 can promote ferroptosis sensitivity in ccRCC cells. Keywords: CX3CL1, Clear cell renal cell carcinoma, Tumor microenvironment, Immunotherapy, Ferroptosis
ISSN:1471-2407
1471-2407
DOI:10.1186/s12885-022-10302-2