An Integrative Pan-Cancer Analysis of the Prognostic and Immunological Role of Casein Kinase 2 Alpha Protein 1 (CSNK2A1) in Human Cancers: A Study Based on Bioinformatics and Immunohistochemical Analysis

Ruohao Wu; Wenting Tang; Kunyin Qiu; Pinggan Li; Yu Li; Dongfang Li; Zhanwen He

doi:10.2147/IJGM.S330500

An Integrative Pan-Cancer Analysis of the Prognostic and Immunological Role of Casein Kinase 2 Alpha Protein 1 (CSNK2A1) in Human Cancers: A Study Based on Bioinformatics and Immunohistochemical Analysis

Int J Gen Med. 2021 Sep 29:14:6215-6232. doi: 10.2147/IJGM.S330500. eCollection 2021.

Authors

Ruohao Wu^#^{1

2}, Wenting Tang^#^{3

4}, Kunyin Qiu^{1

2}, Pinggan Li^{1

2}, Yu Li^{1

2}, Dongfang Li^{1

2}, Zhanwen He^{1

2}

Affiliations

¹ Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong High Education Institutes, Sun Yat-sen Memorial Hospital, Guangzhou, People's Republic of China.
² Department of Pediatrics, Sun Yat-sen Memorial Hospital, Guangzhou, People's Republic of China.
³ State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen Cancer Center, Guangzhou, People's Republic of China.
⁴ Department of Molecular Diagnostics, Sun Yat-sen Cancer Center, Guangzhou, People's Republic of China.

^# Contributed equally.

Abstract

Background: Although emerging animal- or cell-based evidence supports the relationship between casein kinase 2 alpha protein 1 (CSNK2A1) and cancers, no pan-cancer analysis is available. Thus, this report aimed to display the prognostic landscape of CSNK2A1 in pan-cancer and investigate the relationship between CSNK2A1 and tumor immunity.

Methods: In the current study, we investigated the expression pattern, genetic alterations and survival analysis of CSNK2A1 in pan-cancer across multiple datasets and online platforms. The correlations between CSNK2A1 expression and tumor immunity were explored and visualized via R language software. Following this, immunohistochemical (IHC) staining and Kaplan-Meier survival analysis were conducted in clinical patients for proving the bioinformatic findings. Analysis of protein-protein interaction and gene functional enrichment was conducted using GeneMANIA platform and gene set enrichment analysis (GSEA), respectively.

Results: In TCGA, tumor tissue had a higher expression level of CSNK2A1 compared with that in corresponding normal tissue. An increased expression level of CSNK2A1 was related to poor clinical prognosis in most types of cancer such as LIHC. The following expression and survival analysis in clinical liver hepatocellular carcinoma (LIHC) patients confirmed these TCGA findings. CSNK2A1 expression had significant positive correlations with pro-tumor-infiltrating immune cells (TIICs) like M1-macrophages and fibroblasts, and significant negative correlations with anti-tumor-TIICs like activated CD8+ T cells and NK cells, suggesting specific interactions between CSNK2A1 and certain TIICs subtypes. Furthermore, CSNK2A1 expression had the most significant positive correlations with common markers of immune checkpoint including programmed death ligand-1 (PDL1) in LIHC. These findings were validated by an IHC analysis. GSEA analysis demonstrated that high expression of CSNK2A1 was related to cell signaling pathways and immunity-related activities.

Conclusion: These findings suggested that CSNK2A1 was not only related to poor clinical prognosis in cancer like LIHC but also a novel immunotherapy-related biomarker in cancers, especially in LIHC, shedding new light on anti-tumor strategy.

Keywords: casein kinase 2 alpha protein 1; dataset; pan-cancer; survival analysis; tumor immunity; tumor microenvironment.

Grants and funding

This study was supported jointly by the Hygiene Ministry Foundation of Guangdong Province, China (Grant No.4250012039) and the National Natural Science Foundation of China (Grant No.81800155).