Pan-Cancer Analysis Reveals CENPI as a Potential Biomarker and Therapeutic Target in Adrenocortical Carcinoma

Abstract

Background

Centromere protein I (CENPI) has been shown to affect the tumorigenesis of breast and colorectal cancers. However, its biological role and prognostic value in other kinds of cancer, especially adrenocortical carcinoma (ACC), remained to be further investigated.

Methods

Various bioinformatics tools were adopted for exploring the significance of differential expression of CENPI in several malignant tumors from databases such as Depmap portal, GTEx, and TCGA. ACC was selected for further analyzed, and information such as clinicopathological features, the prognostic outcome of diverse subgroups, differentially expressed genes (DEGs), co-expression genes, as well as levels of tumor-infiltrating immune cells (TIIC), was extracted from multiple databases. To verify the possibility of CENPI as a therapeutic target in ACC, drug sensitivity assay and si-RNA mediate knockdown of CENPI were carried out.

Results

The pan-cancer analyses showed that the CENPI mRNA expression levels differed significantly among most cancer types. Additionally, a high precision in cancer prediction and close relation with cancer survival indicated that CENPI could be a potential candidate biomarker to diagnose and predict cancer prognosis. In ACC, CENPI was closely related to multiple clinical characteristics, such as pathological stage and primary therapy outcome. High CENPI levels predicted poor overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) of ACC patients, particularly for different clinical subgroups. Moreover, the expression of CENPI showed positive relationship to Th2 cells but negatively related to most of the TIICs. Furthermore, drug sensitivity assay showed that vorinostat inhibit CENPI expression and ACC cell growth. Additionally, si-RNA mediated knockdown of CENPI inhibited ACC cell growth and invasion and showed synergistic anti-proliferation effect with AURKB inhibitor barasertib.

Conclusion

Pan-cancer analysis demonstrated that CENPI is a potential diagnostic and prognostic biomarker in various cancers as well as an anti-ACC therapeutic target.

Keywords:

• CENPI
• pan-cancer analysis
• diagnosis
• prognostic biomarker
• adrenocortical carcinoma

Data Sharing Statement

All the data in the current work can be acquired from corresponding authors upon request.

Ethical Statement

The present work gained approval from the Ethics Committee of Guangdong Second Provincial General Hospital.

Acknowledgments

The authors gratefully acknowledge the technical support from Meijiayouke Inc. in Wuhan.

Disclosure

All author(s) claimed no competing interests.

Additional information

Funding

The current study was funded by the Doctoral Workstation Foundation of Guangdong Second Provincial General Hospital (No. 2021BSGZ016, 2021BSGZ017, and 2020BSG-2048), Guangzhou Science and Technology Plan Project (No.202102020423, 202201020340 and 202201020485), Foundation of Guangdong Second Provincial General Hospital (No. 2021-KZ-008–01, 3D-B2020014 and TJGC-2021011), Natural Science Foundation of Guangdong Province (No. 2021A1515012329), Guangdong Basic and Applied Basic Research Foundation (No. 2021A1515110430), as well as Key Program for the National Natural Science Foundation of China (No. 82202034).