Browsing by Author "Zhang, Taolan"

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    A breast cancer classification and immune landscape analysis based on cancer stem-cell-related risk panel
    (Springer Nature, 2023-12-08) Hu, Haihong; Zou, Mingxiang; Hu, Hongjuan; Hu, Zecheng; Jiang, Lingxiang; Escobar, David; Zhu, Hongxia; Zhan, Wendi; Yan, Ting; Zhang, Taolan; Radiation Oncology, School of Medicine
    This study sought to identify molecular subtypes of breast cancer (BC) and develop a breast cancer stem cells (BCSCs)-related gene risk score for predicting prognosis and assessing the potential for immunotherapy. Unsupervised clustering based on prognostic BCSC genes was used to determine BC molecular subtypes. Core genes of BC subtypes identified by non-negative matrix factorization algorithm (NMF) were screened using weighted gene co-expression network analysis (WGCNA). A risk model based on prognostic BCSC genes was constructed using machine learning as well as LASSO regression and multivariate Cox regression. The tumor microenvironment and immune infiltration were analyzed using ESTIMATE and CIBERSORT, respectively. A CD79A+CD24-PANCK+-BCSC subpopulation was identified and its spatial relationship with microenvironmental immune response state was evaluated by multiplexed quantitative immunofluorescence (QIF) and TissueFAXS Cytometry. We identified two distinct molecular subtypes, with Cluster 1 displaying better prognosis and enhanced immune response. The constructed risk model involving ten BCSC genes could effectively stratify patients into subgroups with different survival, immune cell abundance, and response to immunotherapy. In subsequent QIF validation involving 267 patients, we demonstrated the existence of CD79A+CD24-PANCK+-BCSC in BC tissues and revealed that this BCSC subtype located close to exhausted CD8+FOXP3+ T cells. Furthermore, both the densities of CD79A+CD24-PANCK+-BCSCs and CD8+FOXP3+T cells were positively correlated with poor survival. These findings highlight the importance of BCSCs in prognosis and reshaping the immune microenvironment, which may provide an option to improve outcomes for patients.
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    Cardiovascular-specific mortality and risk factors in colorectal Cancer patients: A cohort study based on registry data of over 500,000 individuals in the US
    (Elsevier, 2024-02) Zhang, Taolan; Zhu, Hongxia; Hu, Hongjuan; Hu, Haihong; Zhan, Wendi; Jiang, Lingxiang; Tang, Ming; Escobar, David; Huang, Wei; Feng, Yaoguang; Zhou, Junlin; Zou, Mingxiang; Radiation Oncology, School of Medicine
    Background Colorectal cancer (CRC) is one of the most common cancers worldwide, and recent studies have found that CRC patients are at increased risk for cardiovascular disease (CVD). This study aimed to investigate competing causes of death and prognostic factors among a large cohort of CRC patients and to describe cardiovascular-specific mortality in relation to the US standard population. Methods This registry-based cohort study identified patients diagnosed with CRC between 1973 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database in the US. Cumulative mortality functions, conditional standardized mortality ratios, and cause-specific hazard ratios were calculated. Results Of the 563,298 eligible CRC patients included in this study, 407,545 died during the follow-up period. CRC was the leading cause of death, accounting for 49.8% of all possible competing causes of death. CVD was the most common non-cancer cause of death, accounting for 17.8% of total mortality. This study found that CRC patients have a significantly increased risk of cardiovascular-specific mortality compared to the US standard population, with the risk increasing with age and extended survival time. Conclusion This study highlights the need to develop multidisciplinary prevention and management strategies for CRC and CVD to improve CRC patients' survival and quality of life.
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    β-Lapachone promotes the recruitment and polarization of tumor-associated neutrophils (TANs) toward an antitumor (N1) phenotype in NQO1-positive cancers
    (Taylor & Francis, 2024-06-04) Tumbath, Soumya; Jiang, Lingxiang; Li, Xiaoguang; Zhang, Taolan; Zahid, Kashif Rafiq; Zhao, Ye; Zhou, Hao; Yin, Zhijun; Lu, Tao; Jiang, Shu; Chen, Yaomin; Chen, Xiang; Fu, Yang-Xin; Huang, Xiumei; Radiation Oncology, School of Medicine
    NAD(P)H:quinone oxidoreductase 1 (NQO1) is overexpressed in most solid cancers, emerging as a promising target for tumor-selective killing. β-Lapachone (β-Lap), an NQO1 bioactivatable drug, exhibits significant antitumor effects on NQO1-positive cancer cells by inducing immunogenic cell death (ICD) and enhancing tumor immunogenicity. However, the interaction between β-Lap-mediated antitumor immune responses and neutrophils, novel antigen-presenting cells (APCs), remains unknown. This study demonstrates that β-Lap selectively kills NQO1-positive murine tumor cells by significantly increasing intracellular ROS formation and inducing DNA double strand breaks (DSBs), resulting in DNA damage. Treatment with β-Lap efficiently eradicates immunocompetent murine tumors and significantly increases the infiltration of tumor-associated neutrophils (TANs) into the tumor microenvironment (TME), which plays a crucial role in the drug's therapeutic efficacy. Further, the presence of β-Lap-induced antigen medium leads bone marrow-derived neutrophils (BMNs) to directly kill murine tumor cells, aiding in dendritic cells (DCs) recruitment and significantly enhancing CD8+ T cell proliferation. β-Lap treatment also drives the polarization of TANs toward an antitumor N1 phenotype, characterized by elevated IFN-β expression and reduced TGF-β cytokine expression, along with increased CD95 and CD54 surface markers. β-Lap treatment also induces N1 TAN-mediated T cell cross-priming. The HMGB1/TLR4/MyD88 signaling cascade influences neutrophil infiltration into β-Lap-treated tumors. Blocking this cascade or depleting neutrophil infiltration abolishes the antigen-specific T cell response induced by β-Lap treatment. Overall, this study provides comprehensive insights into the role of tumor-infiltrating neutrophils in the β-Lap-induced antitumor activity against NQO1-positive murine tumors.