Identification and verification of the prognostic value of CUL7 in colon adenocarcinoma

Chengxing Wang; Zhenyu Zhao; Yuhao Zhang; Weijun Liang; Chaorong Zhou; Weixing Lin; Yu He; Meimei Wu; Zijie Meng; Yuehua Liao; Min Li; Mariya El Akkawi; Jinglin Zhao; Yaoming He

doi:10.3389/fimmu.2022.1043512

Identification and verification of the prognostic value of CUL7 in colon adenocarcinoma

Front Immunol. 2022 Oct 11:13:1043512. doi: 10.3389/fimmu.2022.1043512. eCollection 2022.

Authors

Chengxing Wang^{1

2}, Zhenyu Zhao², Yuhao Zhang¹, Weijun Liang¹, Chaorong Zhou¹, Weixing Lin¹, Yu He³, Meimei Wu⁴, Zijie Meng⁴, Yuehua Liao⁵, Min Li², Mariya El Akkawi⁶, Jinglin Zhao¹, Yaoming He¹

Affiliations

¹ Department of Gastrointestinal Surgery, Jiangmen Central Hospital, Jiangmen, China.
² The First Affiliated Hospital, Jinan University, Guangzhou, China.
³ National Drug Clinical Trial Institution, Jiangmen Central Hospital, Jiangmen, China.
⁴ Clinical Experimental Center, Jiangmen Key Laboratory of Clinical Biobanks and Translational Research, Jiangmen Central Hospital, Jiangmen, China.
⁵ Department of Pathology, Jiangmen Central Hospital, Jiangmen, China.
⁶ Department of Plastic and Aesthetic Surgery, Zhujiang hospital of Southern Medical University, Guangzhou, China.

Abstract

CUL7, a gene composed of 26 exons associated with cullin 7 protein, is also an E3 ligase that is closely related to cell senescence, apoptosis, and cell transformation and also plays an important role in human cancer. However, there is no systematic pan-cancer analysis has been performed to explore its role in prognosis and immune prediction. In this study, the expression of CUL7 in colon adenocarcinoma (COAD) was investigated to determine its prognosis value. First, based on the Cancer Genome Atlas (TCGA), Genotypic-Tissue Expression Project(GTEx), Cancer Cell Line Encyclopedias(CCLE), and TISIDB database, the potential role of CUL7 in different tumors was explored. Subsequently, the expression of CUL7 in COAD was explored and verified by Immunohistochemistry (IHC). Furthermore, the mutation frequency of CUL7 in COAD was analyzed, and the prognostic value of CUL7 in COAD was discussed. In addition, the nomogram was constructed, and its prognostic value was verified by follow-up data from Jiangmen Central Hospital. Finally, PPI network analysis explored the potential biological function of CUL7 in COAD. The results show that CUL7 is upregulated in most tumors, which is significantly associated with poor survival. At the same time, CUL7 is correlated with the clinical stage and immune landscape of various tumors. In colorectal cancer, CUL7 was overexpressed in tumor tissues by IHC with a mutation frequency of about 4%. CUL7 is an independent prognostic factor for colorectal cancer. The nomogram constructed has effective predictive performance, and external databases proved the prognostic value of CUL7. In addition, PPI network analysis showed that CUL7 was closely related to FBXW8, and further pathway enrichment analysis showed that CUL7 was mainly involved in ubiquitin-mediated proteolysis. Therefore, our study provides a comprehensive understanding of the potential role of CUL7 in different tumors, and CUL7 might be a prognostic marker for COAD.

Keywords: COAD; CUL7; pan-cancer; prognosis; tumor immunity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma* / genetics
Adenocarcinoma* / pathology
Colonic Neoplasms* / genetics
Colonic Neoplasms* / pathology
Cullin Proteins / genetics
Cullin Proteins / metabolism
Humans
Nomograms
Prognosis

Substances

Cullin Proteins
CUL7 protein, human