A Comprehensive Pan-Cancer Analysis of the Regulation and Prognostic Effect of Coat Complex Subunit Zeta 1

Author:

Hong Ye12,Xia Zengfei13ORCID,Sun Yuting14,Lan Yingxia12,Di Tian13,Yang Jing14,Sun Jian5,Qiu Miaozhen14ORCID,Luo Qiuyun6,Yang Dajun13

Affiliation:

1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China

2. Department of Pediatric Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China

3. Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China

4. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China

5. Department of Clinical Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510060, China

6. Department of Cancer Research, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518033, China

Abstract

The Coatomer protein complex Zeta 1 (COPZ1) has been reported to play an essential role in maintaining the survival of some types of tumors. In this study, we sought to explore the molecular characteristics of COPZ1 and its clinical prognostic value through a pan-cancers bioinformatic analysis. We found that COPZ1 was extremely prevalent in a variety of cancer types, and high expression of COPZ1 was linked to poor overall survival in many cancers, while low expression in LAML and PADC was correlated with tumorigenesis. Besides, the CRISPR Achilles’ knockout analysis revealed that COPZ1 was vital for many tumor cells’ survival. We further demonstrated that the high expression level of COPZ1 in tumors was regulated in multi-aspects, including abnormal CNV, DNA-methylation, transcription factor and microRNAs. As for the functional exploration of COPZ1, we found a positive relationship between COPZ1’s expression and stemness and hypoxia signature, especially the contribution of COPZ1 on EMT ability in SARC. GSEA analysis revealed that COPZ1 was associated with many immune response pathways. Further investigation demonstrated that COPZ expression was negatively correlated with immune score and stromal score, and low expression of COPZ1 has been associated to more antitumor immune cell infiltration and pro-inflammatory cytokines. The further analysis of COPZ1 expression and anti-inflammatory M2 cells showed a consistent result. Finally, we verified the expression of COPZ1 in HCC cells, and proved its ability of sustaining tumor growth and invasion with biological experiments. Our study provides a multi-dimensional pan-cancer analysis of COPZ and demonstrates that COPZ1 can serve as both a prospective target for the treatment of cancer and a prognostic marker for a variety of cancer types.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Guangdong

Science and Technology Program of Guangdong

Sun Yat-Sen University cancer center

Publisher

MDPI AG

Subject

Genetics (clinical),Genetics

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