Abstract 3343: Centrosomal and mitotic gene expression profiles across cancer types: Implications for tumor progression and survival outcomes

Abstract Introduction: Genes involved in centrosome function, microtubule dynamics, and mitotic regulation are critical for normal cell division. In cancer, dysregulation of these processes can lead to chromosomal instability and tumor progression. The genes CEP72, HAUS4, TUBGCP4, HAUS2, PLK1, and OFD1 play essential roles in cell cycle regulation, mitosis, and microtubule dynamics, particularly in spindle assembly and centrosome function. These genes are involved in interconnected cellular processes related to mitotic progression, and their altered expression may be linked to cancer progression and survival outcomes. Objective: This study analyzes the expression profiles for these six genes across thirteen cancer types, aiming to identify associations between dysregulation of these genes and cancer progression, as well as their impact on survival outcomes. Methods: We analyzed the expression of these six genes and the tumor suppressor genes APC and PTEN using RNA sequencing data from TCGA cancerous tissues and normal control tissues from GTEx for the thirteen cancer types. Differential gene expression was assessed using the DESeq2 R package, which models RNA sequencing data using a negative binomial distribution. Results: Our analysis identified significant changes in gene expression across cancers, including bladder (BLCA), colon (COAD, READ), esophagus (ESCA), kidney (KICH, KIRC, KIRP), liver (LIHC), prostate (PRAD), stomach (STAD), and thyroid (THCA). Elevated CEP72 expression was associated with lower progression-free survival (PFS). We observed consistent downregulation of CEP72, HAUS2, and PLK1 across several cancers, with significantly adjusted p-values (padj < 1E-5). OFD1, HAUS4, and PTEN showed tissue-specific expression patterns, with upregulation in cancers such as prostate (padj = 1.1E-11) and thyroid (padj = 8.5E-5). We further identified cancer-specific expression profiles for these six genes involved in cell division. These findings suggest complex regulatory mechanisms influencing tumor progression and metastasis. Further analysis of these mitotic and centrosomal proteins revealed significant cancer-specific correlations between gene expression levels of CEP72, HAUS4, TUBGCP4, HAUS2, PLK1, OFD1 and patient outcomes, including PFS, disease-specific survival, and overall survival. Conclusion: This study underscores the interconnectedness of centrosomal and mitotic genes, suggesting that downregulation of key proteins like CEP72, HAUS2, and PLK1 disrupts essential cell migration, proliferation, and adhesion pathways. Conversely, upregulation of HAUS4 may enhance tumor suppressor functions and immune modulation. Analyzing these genes within their broader biological networks provides valuable insights into their roles in cancer progression, offering potential as cancer-specific biomarkers or therapeutic targets. Citation Format: Christopher L. Farrell, Amy Turner, Alex Feltus, Victoria Cipollino. Centrosomal and mitotic gene expression profiles across cancer types: Implications for tumor progression and survival outcomes. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3343.