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CLEC2B and Ferroptosis: The Link Between Psoriatic Arthritis and High Cancer Risk?

CLEC2B, a key gene linked to ferroptosis regulators in psoriatic arthritis, is differentially expressed in a variety of cancers and is associated with immune cell infiltration as well as immune checkpoints.

In patients with psoriatic arthritis (PsA), which is associated with increased cancer risk, the hub gene CLEC2B and ferroptosis may bridge the gap between PsA and the onset of certain malignancies. This is according to a study published in Scientific Reports.1

“This study may provide new research insights into the high cancer risk in patients with psoriatic arthritis,” Xiaoxia Ding, of Zhejiang Provincial People’s Hospital in China, and colleagues, stated. “As a key gene exclusively linked to ferroptosis regulators in psoriatic arthritis, CLEC2B is differentially expressed in a variety of cancers and is closely associated with immune cell infiltration as well as immune checkpoints.”

The incidence of cancer is higher in patients with psoriatic disease, but the cancer-related genomics in these patients is poorly understood. Ferroptosis, which is a form of regulated cell death that is iron- and reactive oxygen species (ROS)-dependent, inhibits tumor formation and/or progression, acting as a promising anticancer pathway. Notably, ROS occurs systemically and locally in psoriasis.

In this study, the researchers used the Gene Expression Omnibus database to obtain whole blood samples from 20 patients with PsA, 20 patients with cutaneous psoriasis, and 12 control patients. Comparisons were made between the control group and the PsA group, along with the PsA group and the cutaneous psoriasis group. Overlapped differentially expressed genes were considered as important genes contributing to PsA development, which were used for further analysis. Ten hub genes and 3 differentially expressed ferroptosis regulators (CISD1, EMC2, CARS) were obtained.

Bioinformatic analysis revealed a correlation between ferroptosis regulator CISD1 and hub gene CLEC2B in the PsA group as well as multiple cancer types. Further, CLEC2B was found to be differently expressed in a variety of malignancies and was linked to prognosis and immune infiltration in a variety of tumors — a finding that the researchers noted was similar to that of prior studies. Therefore, CLEC2B was considered as a key gene that bridges the gap between the development of PsA and cancer through ferroptosis.

“This is the first time that CLEC2B has been found to be associated with the development of psoriatic arthritis through natural killer cells,” the investigators concluded.

Reference:

Li, X, Tao, X and Ding, X. An integrative analysis to reveal that CLEC2B and ferroptosis may bridge the gap between psoriatic arthritis and cancer developmentSci Rep 12, 14653 (2022). https://doi.org/10.1038/s41598-022-19135-2