J Cancer 2021; 12(23):6964-6978. doi:10.7150/jca.63625 This issue

Research Paper

CKS2 Overexpression Correlates with Prognosis and Immune Cell Infiltration in Lung Adenocarcinoma: A Comprehensive Study based on Bioinformatics and Experiments

Zhiping Wang#, Mengyan Zhang#, Yahua Wu, Yilin Yu, Qunhao Zheng, Jiancheng Li

Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China.
#These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Wang Z, Zhang M, Wu Y, Yu Y, Zheng Q, Li J. CKS2 Overexpression Correlates with Prognosis and Immune Cell Infiltration in Lung Adenocarcinoma: A Comprehensive Study based on Bioinformatics and Experiments. J Cancer 2021; 12(23):6964-6978. doi:10.7150/jca.63625. Available from https://www.jcancer.org/v12p6964.htm

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Abstract

Graphic abstract

Objective: Cyclin-dependent kinase regulatory subunit 2 (CKS2) plays a vital role in regulation of the cell cycle and cancer progression. However, the role of CKS2 in lung adenocarcinoma (LUAD) remains unkonwn. Here, we examined the prognostic value and biological functions of CKS2 in LUAD by using omics data of 1,235 LUAD samples from TCGA, GEO, and our own cohort as well as data of in vitro experiments.

Methods: Kaplan-Meier was conducted to evaluate the prognostic value of CKS2 expression. The association between CKS2 expression level and tumor immune infiltration was explored using the single-sample Gene Set Enrichment Analysis (ssGSEA) and TIMER database. Functional enrichment analyses were performed to annotate the biological functions of CKS2 in LUAD. Furthermore, a series of in vitro experiments and immunohistochemistry were performed for validation.

Results: CKS2 overexpression was correlated with the advanced stage, TP53 status, PD-L1 expression, and DNA hypomethylation. Moreover, patients with LUAD and high CKS2 expression exhibited poor overall survival. Functional enrichment analysis indicated that CKS2 was involved in cell division, cell cycle, DNA replication. Experiments in vitro indicated that CKS2 knockdown decreased the invasion and proliferation of LUAD cells and facilitated their apoptosis. ssGSEA and TIMER analysis revealed a negative correlation between CKS2 expression and the immune cell infiltration.

Conclusions: In summary, High CKS2 expression was associated with poor prognosis and low levels of infiltrating immune cells in LUAD as well as with malignant phenotypes. Therefore, CKS2 may be a promising prognostic biomarker and therapeutic target in LUAD.

Keywords: CKS2, lung adenocarcinoma, biomarker, immune infiltration, prognosis, proliferation