CDCA3 is a prognostic biomarker for cutaneous melanoma and is connected with immune infiltration

Tianhao Li; Liquan Wang; Nanze Yu; Ang Zeng; Jiuzuo Huang; Xiao Long

doi:10.3389/fonc.2022.1055308

CDCA3 is a prognostic biomarker for cutaneous melanoma and is connected with immune infiltration

Front Oncol. 2023 Jan 11:12:1055308. doi: 10.3389/fonc.2022.1055308. eCollection 2022.

Authors

Tianhao Li¹, Liquan Wang¹, Nanze Yu¹, Ang Zeng¹, Jiuzuo Huang¹, Xiao Long¹

Affiliation

¹ Department of Plastic and Cosmetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Abstract

Introduction: Dysregulation of cell cycle progression (CCP) is a trait that distinguishes cancer from other diseases. In several cancer types, CCP-related genes serve as the primary risk factor for prognosis, but their role in cutaneous melanoma remains unclear.

Methods: Data from cutaneous melanoma patients were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Using a Wilcoxon test, the level of CCP-related gene expression in cutaneous melanoma patient tissues was compared to that in normal skin tissues. Logistic analysis was then utilized to calculate the connection between the CCP-related genes and clinicopathological variables. The important functions of the CCP-related genes were further investigated using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and single-sample Gene Set Enrichment Analysis (ssGSEA). Univariate and multivariate Cox analyses and Kaplan-Meier analysis were used to estimate the association between CCP-related genes and prognosis. In addition, using Cox multivariate analysis, a nomogram was constructed to forecast the influence of CCP-related genes on survival rates.

Results: High expression of CCP-related genes was associated with TNM stage, age, pathological grade, and Breslow depth (P < 0.05). Multivariate analysis demonstrated that CCP-related genes were an independent factor in overall survival and disease-specific survival. High levels of gene expression originating from CCP were shown by GSEA to trigger DNA replication, the G1-S specific transcription factor, the mitotic spindle checkpoint, and the cell cycle. There was a negative association between CCP-related genes and the abundance of innate immune cells. Finally, we revealed that knockdown of cell division cycle-associated gene 3 (CDCA3) significantly suppressed the proliferation and migration ability of cutaneous melanoma cells.

Conclusion: According to this study, CCP-related genes could serve as potential biomarkers to assess the prognosis of cutaneous melanoma patients and are crucial immune response regulators.

Keywords: GEO; LASSO; TCGA; cell cycle progression derived gene; cell division cycle-associated gene 3; melanoma.

Grants and funding

This study was funded by the National Key R&D Program of China (2020YFE0201600), the Medical Science and Health Technology Innovation Project (2022-I2 M-1-068), the Medical Science and Health Technology Innovation Project (2021-I2 M-1-003) and National High Level Hospital Clinical Research Funding.