Cell Division Cycle-Associated Genes Are Potential Immune Regulators in Nasopharyngeal Carcinoma

Abstract

BackgroundCell division cycle-associated (CDCA) gene family is essential to cell cycle regulation. Numerous studies have illuminated that dysfunction of CDCA genes may not only lead to uncontrolled cell proliferation resulting in tumorigenesis but also influence immune cell infiltration in tumors. However, the role of the CDCA gene family on the prognosis and immune infiltration in nasopharyngeal carcinoma (NPC) remains to be unclear.MethodsSBC human ceRNA array V1.0 was used to measure mRNA expression in three pairs of NPC tissues and nasopharyngitis tissues. The expression of CDCA8 was confirmed in an IHC microarray containing 130 NPC patients. Two external GEO cohorts were enrolled for further analysis. Prognosis analysis was performed using the Kaplan–Meier method. Gene set enrichment analysis (GSEA) was applied to explore the potential mechanism of CDCA genes in NPC. The relationship between CDCA gene family and immune infiltration in NPC was evaluated using the Xcell tool.ResultsCDCA genes were broadly upregulated in NPC tissues compared to nasopharyngitis tissues, and high expression of CDCA3/5/8 indicated worse prognosis in NPC. Besides cell cycle pathways, we found that CDCA3/5/8 were involved in multiple immune-related pathways. Overexpression of CDCA8 was strongly associated with less infiltration of CD8+ T cells and more infiltration of CD4+ Th1 cells and was negatively correlated with immune checkpoint blockade (ICB)-related genes.ConclusionCDCA gene family was upregulated in NPC, and their expressions were associated with adverse prognosis. High expression of CDCA8 was associated not only with poor prognosis, but also with less immune infiltration and downregulation of ICB-related genes in NPC.

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

“…High CDCA3 mRNA expression is substantially linked with several clinicopathologic characteristics in individuals with renal papillary kidney disease, according to Li et al High CDCA3 mRNA expression has been reported to be related to shorter overall survival, progression-free interval, and disease-specific survival (35). Similar results were discovered for malignancies of the lung, prostate, and nasopharynx (14)(15)(16). Overall, CDCA3 is an effective prognostic marker and a promising target for the development of novel anticancer therapies.…”

“…The cell cycle is regulated by a gene family related to cell division. Numerous studies have shown that CDCA gene malfunction can affect immune cell infiltration in tumors and unchecked cell proliferation that results in carcinogenesis ( 14 ). There has also been evidence of increased CDCA3 expression in many cancer types.…”

“…The cell cycle is modulated by a family of genes associated with cell division. A number of studies have indicated that dysfunction of CDCA genes can influence the infiltration of immune cells in tumors as well as cell proliferation, leading to carcinogenesis (14). Studies have suggested increased CDCA3 expression in many cancer types (14)(15)(16).…”

“…A number of studies have indicated that dysfunction of CDCA genes can influence the infiltration of immune cells in tumors as well as cell proliferation, leading to carcinogenesis (14). Studies have suggested increased CDCA3 expression in many cancer types (14)(15)(16). However, the effect of CDCA3 on prognosis in cutaneous melanoma remains unclear.…”

An Integrated Bioinformatics Analysis towards the Identification of Diagnostic, Prognostic, and Predictive Key Biomarkers for Urinary Bladder Cancer

“…Despite the fact that there was some inconsistency, chemotherapy response is connected with a multitude of parameters. The reason for this inconsistency could be owed to the presence of more basal/squamous-like subtypes in the GSE169455 dataset, which have been suggested to suppress chemotherapy efficacy [ 205 ], or to the CDCA8 ′s association with the immune cell infiltration, which could be a predictive biomarker for chemotherapy responsiveness [ 206 , 207 ]. Hence, there is growing evidence that CDCA8 may constitute an effective therapeutic target for prognosis and treatment of BCa, but its exact biological function remains still obscure and needs to be clarified.…”