Pan-cancer analysis reveals the prognostic and immunologic roles of cereblon and its significance for PROTAC design
Si-Han Zhang,
Na Zeng,
Jian-Xuan Sun,
Chen-Qian Liu,
Jin-Zhou Xu,
Meng-Yao Xu,
Ye An,
Xing-Yu Zhong,
Si-Yang Ma,
Hao-Dong He,
Qi-Dong Xia,
Jia Hu,
Shao-Gang Wang
Affiliations
Si-Han Zhang
Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030, Wuhan, China
Na Zeng
Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030, Wuhan, China
Jian-Xuan Sun
Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030, Wuhan, China
Chen-Qian Liu
Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030, Wuhan, China
Jin-Zhou Xu
Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030, Wuhan, China
Meng-Yao Xu
Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030, Wuhan, China
Ye An
Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030, Wuhan, China
Xing-Yu Zhong
Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030, Wuhan, China
Si-Yang Ma
Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030, Wuhan, China
Hao-Dong He
Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030, Wuhan, China
Qi-Dong Xia
Corresponding author.; Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030, Wuhan, China
Jia Hu
Corresponding author.; Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030, Wuhan, China
Shao-Gang Wang
Corresponding author.; Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030, Wuhan, China
Background: Cereblon (CRBN) has emerged as a vital E3 ubiquitin ligase for Proteolysis-targeting chimera (PROTAC) design. However, few studies focus on the physiological mechanism of CRBN, and more studies are needed to explore the influence of CRBN on tumorigenesis. This pan-cancer analysis aims to explore the prognostic and immunologic roles of CRBN, and provide new insight for CRBN into cancer treatment and PROTAC design. Methods: The TCGA database, TIMER 2.0 database, and TISIDB database were used to analyze the role of CRBN in pan-cancer. Multiple bioinformatic methods (ssGSEA, Kaplan-Meier, univariate cox regression, ESTIMATE, CIBERSORT) were applied to investigate the CRBN expression status, gene activity, prognostic values, and its correlation with immune scores, immune infiltration, immune-related functions, HALLMARKs functions, and response to immunotherapy in pan-cancer. Results: In most cancer types, the expression and activity of CRBN in tumor groups were lower compared with normal groups. Upregulated CRBN expression may indicate a better prognosis for cancer patients. The Immune score, stromal score, and tumor purity varied greatly among different cancer types. GSEA analysis showed that high CRBN expression was correlated with the downregulation of tumor-promoting signaling pathways. The level of CRBN was associated with Tumor mutation burden (TMB), Microsatellite instability (MSI), objective response rate (ORR), and immune cell infiltration in a few cancer types. Conclusion: Pan-cancer analysis reveals the potential role of CRBN as a prognostic biomarker and versatile immunologic roles in different cancer types. Upregulated expression of CRBN may be beneficial to CRBN-related immunotherapy and PROTAC design.
