DEP domain containing 1: a potential oncogenic driver

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BACKGROUND: DEP domain-containing protein 1 (DEPDC1) is essential for cell cycle regulation and is increasingly associated with multiple cancers. Accumulating evidence demonstrates that DEPDC1 is significantly upregulated in tumor tissues than in non-malignant tissues across 31 cancer types. DEPDC1 overexpression has been linked to poor prognostic in many cancers, including ACC, KICH, KIRC, KIRP, LGG, LIHC, LUAD, MESO, PAAD, PCPG, SARC, UCEC, and UVM. METHODS: In this study, we analyzed the differential expression of DEPDC1 along with the gene expression profiles associated with it. Specifically, we identified differentially expressed genes (DEGs) associated with higher DEPDC1 expression. These DEGs are involved in key signaling pathways related to cell cycle regulation, DNA damage response, and DNA repair mechanisms across various cancers. RESULTS: The findings show that heightened DEPDC1 expression correlates with significantly upregulated DEGs associated with critical signaling pathways, including Hedgehog, Hippo, MAPK, MYC, NF-KB, Notch, p27, p53, PI3K/AKT, PLK1, RbE2F, TGF-β, WNT, and MCM across numerous cancers. In addition, elevated DEPDC1 levels positively associate with more TH2 cells, which correlate with poor prognosis. Additionally, a strong relationship was identified between DEPDC1 and genes involved in various immune checkpoints (CD80, CD274, CD276, NRP1, CD160, TNFSF15), chemokines (CXCL8, CXCL5, CXCL10, CCL20, CXCL11, CCL7, CXCL9), chemokine receptor (CCR8, CXCR4, CCR1, CCR3, CXCR6, CCR4, CCR5) genes, and DNA mismatch repair (MMR) processes. CONCLUSIONS: These findings underscore the potential of DEPDC1 as a crucial biomarker in cancer prognosis and the biologic pathways modulation. Future studies are necessary to validate the diagnostic and prognostic implications of DEPDC1, enabling the development of targeted therapeutic interventions targeting this protein, which holds promise for enhancing treatment efficacy in cancer patients.

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