Pan-Cancer and Single-Cell Analysis Reveals CENPL as a Cancer Prognosis and Immune Infiltration-Related Biomarker

Ziyang Feng; Yu Chen; Changjing Cai; Jun Tan; Ping Liu; Yihong Chen; Hong Shen; Shan Zeng; Ying Han

doi:10.3389/fimmu.2022.916594

Pan-Cancer and Single-Cell Analysis Reveals CENPL as a Cancer Prognosis and Immune Infiltration-Related Biomarker

Front Immunol. 2022 Jun 30:13:916594. doi: 10.3389/fimmu.2022.916594. eCollection 2022.

Authors

Ziyang Feng^{1

2}, Yu Chen¹, Changjing Cai^{1

2}, Jun Tan³, Ping Liu^{1

2}, Yihong Chen^{1

2}, Hong Shen^{1

2

4}, Shan Zeng^{1

2}, Ying Han^{1

2}

Affiliations

¹ Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
² Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, China.
³ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
⁴ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

Abstract

Background: Centromere protein L (CENPL) is an important member of the centromere protein (CENP) family. However, the correlation between CENPL expression and cancer development and immune infiltration has rarely been studied. Here, we studied the role of CENPL in pan-cancer and further verified the results in lung adenocarcinoma (LUAD) through in vitro experiments.

Methods: The CENPL expression level was studied with TIMER 2.0 and Oncomine databases. The potential value of CENPL as a diagnostic and prognostic biomarker in pan-cancer was evaluated with the TCGA database and GEPIA. The CENPL mutation character was analyzed using the cBioPortal database. The LinkedOmics and CancerSEA databases were used to carry out the function analysis of CENPL. The role of CENPL in immune infiltration was studied using the TIMER and TISIDB websites. Moreover, the expression of CENPL was detected through RT-qPCR and Western blotting. Immunohistochemistry was used to evaluate the infiltration level of CD8⁺ T cells. Cell proliferation was detected by EdU and CCK8. A flow cytometer was used to analyze the influence of CENPL in cell cycle and apoptosis.

Results: CENPL was increased in most of the cancers. The upregulation and mutation of CENPL were associated with a poorer prognosis in many cancers. The results showed a significant positive correlation between CENPL and myeloid-derived suppressor cell (MDSC) infiltration and a negative correlation between CENPL and T-cell NK infiltration in most of the cancers. CENPL regulated cell proliferation and cell cycle, and was negatively correlated with the inflammation level of LUAD. The in vitro experiments suggested that CENPL was increased in LUAD tissue and cell lines. There was a negative correlation between CENPL expression and CD8⁺ T-cell infiltration. The knockdown of CENPL significantly suppressed the expression of CDK2 and CCNE2, and induced G0/G1 arrest and apoptosis of LUAD.

Conclusions: CENPL may function as a potential biomarker and oncogene in pan-cancer, especially LUAD. Furthermore, CENPL was associated with immune cell infiltration in pan-cancer, providing a potential immune therapy target for tumor treatment.

Keywords: CENPL; G0/G1 arrest; LUAD; apoptosis; immune infiltration; pan-cancer.

Publication types

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

MeSH terms

Adenocarcinoma of Lung* / genetics
Biomarkers, Tumor / metabolism
CD8-Positive T-Lymphocytes / metabolism
Cell Cycle Proteins / metabolism
Chromosomal Proteins, Non-Histone / metabolism
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms* / pathology
Prognosis
Single-Cell Analysis

Substances

Biomarkers, Tumor
CENPL protein, human
Cell Cycle Proteins
Chromosomal Proteins, Non-Histone