4.6 Article

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

Journal

FRONTIERS IN ONCOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2022.1055308

Keywords

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

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This study found that CCP-related genes are associated with TNM stage, age, pathological grade, and Breslow depth in cutaneous melanoma patients. These genes play a crucial role in disease prognosis. Further analysis revealed their involvement in DNA replication, G1-S specific transcription factor, mitotic spindle checkpoint, and cell cycle. Moreover, there is a negative association between CCP-related genes and the abundance of innate immune cells. Knockdown of CDCA3, a CCP-related gene, significantly suppressed the proliferation and migration ability of cutaneous melanoma cells.
IntroductionDysregulation 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. MethodsData 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. ResultsHigh 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. ConclusionAccording 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.

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