Browsing by Author "Zou, Ming-Xiang"

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    Clinicopathological and Prognostic Characteristics in Dedifferentiated/Poorly Differentiated Chordomas: A Pooled Analysis of Individual Patient Data From 58 Studies and Comparison With Conventional Chordomas
    (Frontiers Media, 2021-08-13) Liu, Fu-Sheng; Zheng, Bo-Wen; Zhang, Tao-Lan; Li, Jing; Lv, Guo-Hua; Yan, Yi-Guo; Huang, Wei; Zou, Ming-Xiang; Radiation Oncology, School of Medicine
    Background: Currently, the clinicopathological and prognostic characteristics of dedifferentiated chordoma (DC) and poorly differentiated chordoma (PDC) remain poorly understood. In this study, we sought to characterize clinicopathological parameters in a large PDC/DC cohort and determine their correlations with progression-free survival (PFS) and overall survival (OS) of patients. We also attempted to compare clinical features between PDC/DC and conventional chordoma (CC). Methods: Literature searches (from inception to June 01, 2020) using Medline, Embase, Google Scholar and Wanfang databases were conducted to identify eligible studies according to predefined criteria. The local database at our center was also retrospectively reviewed to include CC patients for comparative analysis. Results: Fifty-eight studies from the literature and 90 CC patients from our local institute were identified; in total, 54 PDC patients and 96 DC patients were analyzed. Overall, PDC or DC had distinct characteristics from CC, while PDC and DC shared similar clinical features. Adjuvant radiotherapy and chemotherapy were associated with both PFS and OS in PDC patients in the univariate and/or multivariate analyses. In the DC cohort, tumor resection type, adjuvant chemotherapy and tumor dedifferentiation components significantly affected PFS, whereas none of them were predictive of outcome in the multivariate analysis. By analyzing OS, we found that surgery, resection type and the time to dedifferentiation predicted the survival of DC patients; however, only surgery remained significant after adjusting for other covariables. Conclusions: These data may offer useful information to better understand the clinical characteristics of PDC/DC and may be helpful in improving the outcome prediction of patients.
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    Clinicopathological and Prognostic Characteristics in Spinal Chondroblastomas: A Pooled Analysis of Individual Patient Data From a Single Institute and 27 Studies
    (Sage, 2023) Zheng, Bo-Wen; Huang, Wei; Liu, Fu-Sheng; Zhang, Tao-Lan; Wang, Xiao-Bin; Li, Jing; Lv, Guo-Hua; Yan, Yi-Guo; Zou, Ming-Xiang; Radiation Oncology, School of Medicine
    Study design: Retrospective pooled analysis of individual patient data. Objectives: Spinal chondroblastoma (CB) is a very rare pathology and its clinicopathological and prognostic features remain unclear. Here, we sought to characterize the clinicopathological data of a large spinal CB cohort and determine factors affecting the local recurrence-free survival (LRFS) and overall survival (OS) of patients. Methods: Electronic searches using Medline, Embase, Google Scholar and Wanfang databases were performed to identify eligible studies per predefined criteria. A retrospective review was also conducted to include additional patients at our center. Results: Twenty-seven studies from the literature and 8 patients from our local institute were identified, yielding a total of 61 patients for analysis. Overall, there were no differences in clinicopathological characteristics between the local and literature cohorts, except for absence or presence of spinal canal invasion by tumor on imagings and chicken-wire calcification in tumor tissues. Univariate Kaplan-Meier analysis revealed that previous treatment, preoperative or postoperative neurological deficits, type of tumor resection, secondary aneurysmal bone cyst (ABC), chicken-wire calcification and radiotherapy correlated closely with LRFS, though only type of tumor resection, chicken-wire calcification and radiotherapy were predictive of outcome based on multivariate Cox analysis. Analyzing OS, we found that a history of preoperative treatment, concurrent ABC, chicken-wire calcification, type of tumor resection and adjuvant radiotherapy had a significant association with survival, whereas only type of tumor resection remained statistically significant after adjusting for other covariables. Conclusion: These data may be helpful in prognostic risk stratification and individualized therapy decision making for patients.
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    Hypoxic Upregulation of IER2 Increases Paracrine GMFG Signaling of Endoplasmic Reticulum Stress-CAF to Promote Chordoma Progression via Targeting ITGB1
    (Wiley, 2024) Zhang, Tao-Lan; Zheng, Bo-Wen; Xia, Chao; Wu, Peng-Fei; Zheng, Bo-Yv; Jiang, Ling-Xiang; Li, Jing; Lv, Guo-Hua; Zhou, Hong; Huang, Wei; Zou, Ming-Xiang; Radiation Oncology, School of Medicine
    Currently, the oncogenic mechanism of endoplasmic reticulum stress-CAF (ERS-CAF) subpopulation in chordoma remains unknown. Here, single-cell RNA sequencing, spatial transcriptomics, GeoMx Digital Spatial Profiler, data-independent acquisition proteomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence are used to unveil the precise molecular mechanism of how ERS-CAF affected chordoma progression. Results show that hypoxic microenvironment reprograms CAFs into ERS-CAF subtype. Mechanistically, this occurrs via hypoxia-mediated transcriptional upregulation of IER2. Overexpression of IER2 in CAFs promotes chordoma progression, which can be impeded by IER2 knockdown or use of ERS inhibitors. IER2 also induces expression of ERS-CAF marker genes and results in production of a pro-tumorigenic paracrine GMFG signaling, which exert its biological function via directly binding to ITGB1 on tumor cells. ITGB1 inhibition attenuates tumor malignant progression, which can be partially reversed by exogenous GMFG intervention. Further analyses reveal a positive correlation between ITGB1high tumor cell counts and SPP1+ macrophage density, as well as the spatial proximity of these two cell types. Clinically, a significant correlation of high IER2/ITGB1 expression with tumor aggressive phenotype and poor patient survival is observed. Collectively, the findings suggest that ERS-CAF regulates SPP1+ macrophage to aggravate chordoma progression via the IER2/GMFG/ITGB1 axis, which may be targeted therapeutically in future.
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    Integrating single-cell and spatial transcriptomics reveals endoplasmic reticulum stress-related CAF subpopulations associated with chordoma progression
    (Oxford University Press, 2024) Zhang, Tao-Lan; Xia, Chao; Zheng, Bo-Wen; Hu, Hai-Hong; Jiang, Ling-Xiang; Escobar, David; Zheng, Bo-Yv; Chen, Tian-Dong; Li, Jing; Lv, Guo-Hua; Huang, Wei; Yan, Yi-Guo; Zou, Ming-Xiang; Radiation Oncology, School of Medicine
    Background: With cancer-associated fibroblasts (CAFs) as the main cell type, the rich myxoid stromal components in chordoma tissues may likely contribute to its development and progression. Methods: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence (QIF) were used to dissect the heterogeneity, spatial distribution, and clinical implication of CAFs in chordoma. Results: We sequenced here 72 097 single cells from 3 primary and 3 recurrent tumor samples, as well as 3 nucleus pulposus samples as controls using scRNA-seq. We identified a unique cluster of CAF in recurrent tumors that highly expressed hypoxic genes and was functionally enriched in endoplasmic reticulum stress (ERS). Pseudotime trajectory and cell communication analyses showed that this ERS-CAF subpopulation originated from normal fibroblasts and widely interacted with tumoral and immune cells. Analyzing the bulk RNA-seq data from 126 patients, we found that the ERS-CAF signature score was associated with the invasion and poor prognosis of chordoma. By integrating the results of scRNA-seq with spatial transcriptomics, we demonstrated the existence of ERS-CAF in chordoma tissues and revealed that this CAF subtype displayed the most proximity to its surrounding tumor cells. In subsequent QIF validation involving 105 additional patients, we confirmed that ERS-CAF was abundant in the chordoma microenvironment and located close to tumor cells. Furthermore, both ERS-CAF density and its distance to tumor cells were correlated with tumor malignant phenotype and adverse patient outcomes. Conclusions: These findings depict the CAF landscape for chordoma and may provide insights into the development of novel treatment approaches.
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    Prognostic Significance of Tumor-Associated Macrophages in Chondroblastoma and Their Association with Response to Adjuvant Radiotherapy
    (Dovepress, 2021-05-17) Zheng, Bo-Wen; Yang, Min-Liang; Huang, Wei; Zheng, Bo-Yv; Zhang, Tao-Lan; Li, Jing; Lv, Guo-Hua; Yan, Yi-Guo; Zou, Ming-Xiang; Radiation Oncology, School of Medicine
    Objective: Chondroblastoma (CB) is a rare and locally growing cartilage-derived tumor. Currently, clinical implications of tumor-associated macrophages (TAMs) in CB remain unclear. In this study, we sought to analyze the relationship between TAM parameters (including densities of CD68+ and CD163+ cells as well as the CD163+/CD68+ ratio) and clinicopathological characteristics and survival of patients. Methods: Immunohistochemistry was used to assess TAM subtypes for CD68 and CD163, as well as the expression levels of p53, CD34, and Ki-67 on tumor cells in 132 tissue specimens retrieved between July 2002 and April 2020. Then, TAM parameters were retrospectively analyzed for their associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]) and clinicopathological features. Results: TAM densities were significantly higher in axial chondroblastoma tissue than in extra-axial chondroblastoma tissue. Moreover, the number of CD163+ TAMs was positively correlated with tumor invasion of surrounding tissues and high expression of CD34 and Ki-67 on tumor cells, whereas CD163+ cell density and the CD163/CD68 ratio were negatively associated with patient response to adjuvant radiotherapy. Univariate Kaplan-Meier analysis revealed that the number of CD68+ and CD163+ lymphocytes was significantly associated with both LRFS and OS. Multivariate Cox regression analysis showed that CD163+ and CD68+ cell levels were independent prognostic factors of LRFS, while TAM data independently predicted OS. More importantly, in subgroup analysis based on three significant factors in univariate survival analysis (including tumor location, adjuvant radiotherapy, and surrounding tissue invasion by tumors), the TAM parameters still displayed good prognostic performance. Conclusion: These data suggest that TAM may significantly affect the biological behavior of CB. We hypothesize that modulating the TAM level or polarization status in the microenvironment may be an effective approach for CB treatment.