2. Academic Validation
  3. CX3CL1 promotes cell sensitivity to ferroptosis and is associated with the tumor microenvironment in clear cell renal cell carcinoma

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

  • BMC Cancer. 2022 Nov 17;22(1):1184. doi: 10.1186/s12885-022-10302-2.
Qiming Gong # 1,  Zhiting Guo # 2,  Wenjuan Sun 3,  Xiuri Du 4,  Yan Jiang # 5,  Fahui Liu # 6
Affiliations

Affiliations

  • 1 Department of Nephrology, Affiliated Hospital of Youjiang Medical University for Nationalities, No.18 Zhongshan Road, Baise, 533000, Guangxi, China.
  • 2 College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350108, China.
  • 3 Department of Internal Medicine, Chonnam National University Medical School, Gwangju, 61469, South Korea.
  • 4 Department of Rheumatology, Affiliated Hospital of Youjiang Medical University for Nationalities, No.18 Zhongshan Road, Baise, 533000, Guangxi, China.
  • 5 Science Laboratory, Youjiang Medical University for Nationalities, No.98 Chengxiang Road, Baise, 533000, Guangxi, China. jiangyan9hr@yeah.net.
  • 6 Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, 40530, Gothenburg, Sweden. liufahui005@163.com.
  • # Contributed equally.
PMID: 36397015 DOI: 10.1186/s12885-022-10302-2
Abstract

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+ 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; Ferroptosis; Immunotherapy; Tumor microenvironment.

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