Browsing by Author "Zeng, Ziyu"

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    CDHu40: a novel marker gene set of neuroendocrine prostate cancer
    (Oxford University Press, 2024) Liu, Sheng; Nam, Hye Seung; Zeng, Ziyu; Deng, Xuehong; Pashaei, Elnaz; Zang, Yong; Yang, Lei; Li, Chenglong; Huang, Jiaoti; Wendt, Michael K.; Lu, Xin; Huang, Rong; Wan, Jun; Medical and Molecular Genetics, School of Medicine
    Prostate cancer (PCa) is the most prevalent cancer affecting American men. Castration-resistant prostate cancer (CRPC) can emerge during hormone therapy for PCa, manifesting with elevated serum prostate-specific antigen levels, continued disease progression, and/or metastasis to the new sites, resulting in a poor prognosis. A subset of CRPC patients shows a neuroendocrine (NE) phenotype, signifying reduced or no reliance on androgen receptor signaling and a particularly unfavorable prognosis. In this study, we incorporated computational approaches based on both gene expression profiles and protein-protein interaction networks. We identified 500 potential marker genes, which are significantly enriched in cell cycle and neuronal processes. The top 40 candidates, collectively named CDHu40, demonstrated superior performance in distinguishing NE PCa (NEPC) and non-NEPC samples based on gene expression profiles. CDHu40 outperformed most of the other published marker sets, excelling particularly at the prognostic level. Notably, some marker genes in CDHu40, absent in the other marker sets, have been reported to be associated with NEPC in the literature, such as DDC, FOLH1, BEX1, MAST1, and CACNA1A. Importantly, elevated CDHu40 scores derived from our predictive model showed a robust correlation with unfavorable survival outcomes in patients, indicating the potential of the CDHu40 score as a promising indicator for predicting the survival prognosis of those patients with the NE phenotype. Motif enrichment analysis on the top candidates suggests that REST and E2F6 may serve as key regulators in the NEPC progression.
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    Comparative Analysis of 3D Culture Methodologies in Prostate Cancer Cells
    (bioRxiv, 2025-03-13) Foster, Ella; Wardhana, Oliver; Zeng, Ziyu; Lu, Xin; Medicine, School of Medicine
    Three-dimensional (3D) cell culture models are increasingly utilized in cancer research to better replicate in vivo tumor microenvironments. This study examines the effects of different 3D scaffolding materials, including Matrigel, GelTrex, and the plant-based GrowDex, on prostate cancer cell lines, with a particular emphasis on neuroendocrine prostate cancer (NEPC). Four cell lines (LNCaP, LASCPC-01, PC-3, and KUCaP13) were cultured in these scaffolds to evaluate spheroid formation, cell viability, and gene expression. The results revealed that while all scaffolds supported cell viability, spheroid formation varied significantly: Matrigel promoted the most robust spheroids, especially for LASCPC-01, whereas GrowDex exhibited limitations for certain cell lines. Gene expression analysis indicated a consistent reduction in androgen receptor (AR) expression in LNCaP cells across all scaffolds, suggesting a potential shift towards a neuroendocrine phenotype. However, the expression of neuroendocrine markers varied depending on the scaffold and culture method, with the mini-domes method in Matrigel leading to decreased expression of both castration-resistant prostate cancer (CRPC) and NEPC markers. These findings highlight the scaffold-dependent variability in 3D culture outcomes and emphasize the need for standardized methodologies to ensure consistency and relevance in prostate cancer research.
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    Neutrophils Resist Ferroptosis and Promote Breast Cancer Metastasis through Aconitate Decarboxylase 1
    (Elsevier, 2023) Zhao, Yun; Liu, Zhongshun; Liu, Guoqiang; Zhang, Yuting; Liu, Sheng; Gan, Dailin; Chang, Wennan; Peng, Xiaoxia; Sung, Eun Suh; Gilbert, Keegan; Zhu, Yini; Wang, Xuechun; Zeng, Ziyu; Baldwin, Hope; Ren, Guanzhu; Weaver, Jessica; Huron, Anna; Mayberry, Toni; Wang, Qingfei; Wang, Yujue; Diaz-Rubio, Maria Elena; Su, Xiaoyang; Stack, M. Sharon; Zhang, Siyuan; Lu, Xuemin; Sheldon, Ryan D.; Li, Jun; Zhang, Chi; Wan, Jun; Lu, Xin; Medical and Molecular Genetics, School of Medicine
    Metastasis causes breast cancer-related mortality. Tumor-infiltrating neutrophils (TINs) inflict immunosuppression and promote metastasis. Therapeutic debilitation of TINs may enhance immunotherapy, yet it remains a challenge to identify therapeutic targets highly expressed and functionally essential in TINs but under-expressed in extra-tumoral neutrophils. Here, using single-cell RNA sequencing to compare TINs and circulating neutrophils in murine mammary tumor models, we identified aconitate decarboxylase 1 (Acod1) as the most upregulated metabolic enzyme in mouse TINs and validated high Acod1 expression in human TINs. Activated through the GM-CSF-JAK/STAT5-C/EBPβ pathway, Acod1 produces itaconate, which mediates Nrf2-dependent defense against ferroptosis and upholds the persistence of TINs. Acod1 ablation abates TIN infiltration, constrains metastasis (but not primary tumors), bolsters antitumor T cell immunity, and boosts the efficacy of immune checkpoint blockade. Our findings reveal how TINs escape from ferroptosis through the Acod1-dependent immunometabolism switch and establish Acod1 as a target to offset immunosuppression and improve immunotherapy against metastasis.