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  1. Article ; Online: UCseek

    Ping Wang / Yue Shi / Jianye Zhang / Jianzhong Shou / Mingxin Zhang / Daojia Zou / Yuan Liang / Juan Li / Yezhen Tan / Mei Zhang / Xingang Bi / Liqun Zhou / Weimin Ci / Xuesong Li

    EBioMedicine, Vol 89, Iss , Pp 104437- (2023)

    ultrasensitive early detection and recurrence monitoring of urothelial carcinoma by shallow-depth genome-wide bisulfite sequencing of urinary sediment DNAResearch in context

    2023  

    Abstract: Summary: Background: Current methods for the detection and surveillance of urothelial carcinomas (UCs) are often invasive, costly, and not effective for low-grade, early-stage, and minimal residual disease (MRD) tumors. We aimed to develop and validate a ...

    Abstract Summary: Background: Current methods for the detection and surveillance of urothelial carcinomas (UCs) are often invasive, costly, and not effective for low-grade, early-stage, and minimal residual disease (MRD) tumors. We aimed to develop and validate a model from urine sediments to predict different grade and stage UCs with low cost and high accuracy. Methods: We collected 167 samples, including 90 tumors and 77 individuals without tumors, as a discovery cohort. We assessed copy number variations and methylation values for them and constructed a diagnostic classifier to detect UC, UCseek, by using an individual read-based method and support vector machine. The performance of UCseek was validated in an independent cohort derived from three hospitals (n = 206) and a relapse cohort (n = 42) for monitoring recurrence. Findings: We constructed UCseek, which could predict UCs with high sensitivity (92.7%), high specificity (90.7%), and high accuracy (91.7%) in the independent validation set. The accuracy of UCseek in low-grade and early-stage patients reached 91.8% and 94.3%, respectively. Notably, UCseek retained great performance at ultralow sequencing depths (0.3X-0.5X). It also demonstrated a powerful ability to monitor recurrence in a surveillance cohort compared with cystoscopy (90.91% vs. 59.09%). Interpretation: We optimized an improved approach named UCseek for the noninvasive diagnosis and monitoring of UCs in both low- and high-grade tumors and in early- and advanced-stage tumors, even at ultralow sequencing depths, which may reduce the burden of cystoscopy and blind second surgery. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgments section.
    Keywords Urothelial carcinoma ; Molecular diagnostics ; Tumor markers ; Diagnosis ; Relapse monitoring ; Machine learning ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 616
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The RNA N6-Methyladenosine Methyltransferase METTL3 Promotes the Progression of Kidney Cancer via N6-Methyladenosine-Dependent Translational Enhancement of ABCD1

    Yue Shi / Yanliang Dou / Jianye Zhang / Jie Qi / Zijuan Xin / Mingxin Zhang / Yu Xiao / Weimin Ci

    Frontiers in Cell and Developmental Biology, Vol

    2021  Volume 9

    Abstract: The role of N6-methyladenosine (m6A)-modifying proteins in cancer progression depends on the cell type and mRNA affected. However, the biological role and underlying mechanism of m6A in kidney cancer is limited. Here, we discovered the variability in m6A ...

    Abstract The role of N6-methyladenosine (m6A)-modifying proteins in cancer progression depends on the cell type and mRNA affected. However, the biological role and underlying mechanism of m6A in kidney cancer is limited. Here, we discovered the variability in m6A methyltransferase METTL3 expression was significantly increased in clear cell renal cell carcinoma (ccRCC) the most common subtype of renal cell carcinoma (RCC), and high METTL3 expression predicts poor prognosis in ccRCC patients using a dataset from The Cancer Genome Atlas (TCGA). Importantly, knockdown of METTL3 in ccRCC cell line impaired both cell migration capacity and tumor spheroid formation in soft fibrin gel, a mechanical method for selecting stem-cell-like tumorigenic cells. Consistently, overexpression of METTL3 but not methyltransferase activity mutant METTL3 can promote cell migration, spheroid formation in cell line and tumor growth in xenograft model. Transcriptional profiling of m6A in ccRCC tissues identified the aberrant m6A transcripts were enriched in cancer-related pathways. Further m6A-sequencing of METTL3 knockdown cells and functional studies confirmed that translation of ABCD1, an ATP-binding cassette (ABC) transporter of fatty acids, was inhibited by METTL3 in m6A-dependent manner. Moreover, knockdown of ABCD1 in ccRCC cells decreased cancer cell migration and spheroid formation, and upregulation of ABCD1 acts as an adverse prognosis factor of kidney cancer patients. In summary, our study identifies that METTL3 promotes ccRCC progression through m6A modification-mediated translation of ABCD1, providing an epitranscriptional insight into the molecular mechanism in kidney cancer.
    Keywords METTL3 ; kidney cancer ; m6A ; ABCD1 ; cancer progression ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Single-Nucleotide Resolution Mapping of N6‑Methyladenine in Genomic DNA

    Cheng-Jie Ma / Gaojie Li / Wen-Xuan Shao / Yi-Hao Min / Ping Wang / Jiang-Hui Ding / Neng-Bin Xie / Min Wang / Feng Tang / Yu-Qi Feng / Weimin Ci / Yinsheng Wang / Bi-Feng Yuan

    ACS Central Science, Vol 9, Iss 9, Pp 1799-

    2023  Volume 1809

    Keywords Chemistry ; QD1-999
    Language English
    Publishing date 2023-08-01T00:00:00Z
    Publisher American Chemical Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Metabolism-Related Signature Analysis Uncovers the Prognostic and Immunotherapeutic Characteristics of Renal Cell Carcinoma

    Jianye Zhang / Qi Zhang / Yue Shi / Ping Wang / Yanqing Gong / Shiming He / Zhihua Li / Ninghan Feng / Yang Wang / Peng Jiang / Weimin Ci / Xuesong Li / Liqun Zhou

    Frontiers in Molecular Biosciences, Vol

    2022  Volume 9

    Abstract: Renal cell carcinoma (RCC) is one of the most common urological cancers. RCC has a poor prognosis and is considered a metabolic disease. It has been reported that many metabolic pathways are associated with the development of RCC. However, the prognostic ...

    Abstract Renal cell carcinoma (RCC) is one of the most common urological cancers. RCC has a poor prognosis and is considered a metabolic disease. It has been reported that many metabolic pathways are associated with the development of RCC. However, the prognostic value of metabolism-related genes in RCC is unclear. We herein aimed to establish a scoring system based on the gene expression profile of metabolic genes to evaluate the response to immunotherapy and predict the prognosis of RCC. In this study, we collected multicentre RCC data and performed integrated analysis to characterize the role of tumour metabolism in RCC and explore the relationship between metabolism and prognosis and immune therapy. Based on transcriptomic data, metabolism-related genes were used for nonnegative matrix factorization clustering. We obtained three subclasses of RCC (M1, M2, and M3), and they are associated with different prognoses and immune infiltrate levels. Then, based on the pathway activity of 113 metabolism-related gene signatures, we classified patients into three distinct metabolism-related signatures. Finally, we provide a metabolism-related pathway score (MRPScore) that is significantly associated with RCC prognosis and the response to immunotherapy. Taken together, in this study, we established an RCC classification system based on metabolic gene expression profiles that could further the understanding of the diversity of RCC. We also present the MRPScore, which may be used as an indicator to predict the response to clinical immune therapy.
    Keywords renal cell carcinoma ; metabolism ; MRPScore ; prognosis ; immunotherapy ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Decoding the multicellular ecosystem of vena caval tumor thrombus in clear cell renal cell carcinoma by single-cell RNA sequencing

    Yue Shi / Qi Zhang / Hai Bi / Min Lu / Yezhen Tan / Daojia Zou / Liyuan Ge / Zhigang Chen / Cheng Liu / Weimin Ci / Lulin Ma

    Genome Biology, Vol 23, Iss 1, Pp 1-

    2022  Volume 22

    Abstract: Abstract Background Vascular invasion with tumor thrombus frequently occurs in advanced renal cell carcinoma (RCC). Thrombectomy is one of the most challenging surgeries with high rate of perioperative morbidity and mortality. However, the mechanisms ... ...

    Abstract Abstract Background Vascular invasion with tumor thrombus frequently occurs in advanced renal cell carcinoma (RCC). Thrombectomy is one of the most challenging surgeries with high rate of perioperative morbidity and mortality. However, the mechanisms driving tumor thrombus formation are poorly understood which is required for designing effective therapy for eliminating tumor thrombus. Results We perform single-cell RNA sequencing analysis of 19 surgical tissue specimens from 8 clear cell renal cell carcinoma (ccRCC) patients with tumor thrombus. We observe tumor thrombus has increased tissue resident CD8+ T cells with a progenitor exhausted phenotype compared with the matched primary tumors. Remarkably, macrophages, malignant cells, endothelial cells and myofibroblasts from TTs exhibit enhanced remodeling of the extracellular matrix. The macrophages and malignant cells from primary tumors represent proinflammatory states, but also increase the expression of immunosuppressive markers compared to tumor thrombus. Finally, differential gene expression and interaction analyses reveal that tumor-stroma interplay reshapes the extracellular matrix in tumor thrombus associated with poor survival. Conclusions Our comprehensive picture of the ecosystem of ccRCC with tumor thrombus provides deeper insights into the mechanisms of tumor thrombus formation, which may aid in the design of effective neoadjuvant therapy to promote downstaging of tumor thrombus and decrease the perioperative morbidity and mortality of thrombectomy.
    Keywords Tumor thrombus ; Clear cell renal cell carcinoma ; Single-cell RNA sequencing ; Tumor heterogeneity ; Tumor microenvironment ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Single‐Cell RNA‐seq Reveals a Developmental Hierarchy Super‐Imposed Over Subclonal Evolution in the Cellular Ecosystem of Prostate Cancer

    Guangzhe Ge / Yang Han / Jianye Zhang / Xinxin Li / Xiaodan Liu / Yanqing Gong / Zhentao Lei / Jie Wang / Weijie Zhu / Yangyang Xu / Yiji Peng / Jianhua Deng / Bao Zhang / Xuesong Li / Liqun Zhou / Huiying He / Weimin Ci

    Advanced Science, Vol 9, Iss 15, Pp n/a-n/a (2022)

    2022  

    Abstract: Abstract Prostate cancer (PCa) is a complex disease. An ongoing accumulation of mutations results in increased genetic diversity, with the tumor acquiring distinct subclones. However, non‐genetic intra‐tumoral heterogeneity, the cellular differentiation ... ...

    Abstract Abstract Prostate cancer (PCa) is a complex disease. An ongoing accumulation of mutations results in increased genetic diversity, with the tumor acquiring distinct subclones. However, non‐genetic intra‐tumoral heterogeneity, the cellular differentiation state and the interplay between subclonal evolution and transcriptional heterogeneity are poorly understood. Here, the authors perform single‐cell RNA sequencing from 14 untreated PCa patients. They create an extensive cell atlas of the PCa patients and mapped developmental states onto tumor subclonal evolution. They identify distinct subclones across PCa patients and then stratify tumor cells into four transcriptional subtypes, EMT‐like (subtype 0), luminal A‐like (subtype 1), luminal B/C‐like (subtype 2), and basal‐like (subtype 3). These subtypes are hierarchically organized into stem cell‐like and differentiated status. Strikingly, multiple subclones within a single primary tumor present with distinct combinations of preferential subtypes. In addition, subclones show different communication strengths with other cell types within the tumor ecosystem, which may modulate the distinct transcriptional subtypes of the subclones. Notably, by integrating TCGA data, they discover that both tumor cell transcriptional heterogeneity and cellular ecosystem diversity correlate with features of a poor prognosis. Collectively, their study provides the analysis of subclonal and transcriptional heterogeneity and its implication for patient prognosis.
    Keywords cellular ecosystem ; epithelial‐to‐mesenchymal transition ; prostate cancer ; subtype ; transcriptional heterogeneity ; tumor subclone ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Vitamin C increases 5-hydroxymethylcytosine level and inhibits the growth of bladder cancer

    Ding Peng / Guangzhe Ge / Yanqing Gong / Yonghao Zhan / Shiming He / Bao Guan / Yifan Li / Ziying Xu / Han Hao / Zhisong He / Gengyan Xiong / Cuijian Zhang / Yue Shi / Yuanyuan Zhou / Weimin Ci / Xuesong Li / Liqun Zhou

    Clinical Epigenetics, Vol 10, Iss 1, Pp 1-

    2018  Volume 13

    Abstract: Abstract Background 5-Hydroxymethylcytosine (5hmC) is converted from 5-methylcytosine (5mC) by a group of enzymes termed ten-eleven translocation (TET) family dioxygenases. The loss of 5hmC has been identified as a hallmark of most types of cancer and is ...

    Abstract Abstract Background 5-Hydroxymethylcytosine (5hmC) is converted from 5-methylcytosine (5mC) by a group of enzymes termed ten-eleven translocation (TET) family dioxygenases. The loss of 5hmC has been identified as a hallmark of most types of cancer and is related to tumorigenesis and progression. However, the role of 5hmC in bladder cancer is seldom investigated. Vitamin C was recently reported to induce the generation of 5hmC by acting as a cofactor for TET dioxygenases. In this study, we explored the role of 5hmC in bladder cancer and the therapeutic efficacy of vitamin C in increasing the 5hmC pattern. Results 5hmC was decreased in bladder cancer samples and was related to patient overall survival. Genome-wide mapping of 5hmC in tumor tissues and vitamin C-treated bladder cancer cells revealed that 5hmC loss was enriched in cancer-related genes and that vitamin C treatment increased 5hmC levels correspondingly. Vitamin C treatment shifted the transcriptome and inhibited the malignant phenotypes associated with bladder cancer cells in both in vitro cell lines and in vivo xenografts. Conclusions This study provided mechanistic insights regarding the 5hmC loss in bladder cancer and a rationale for exploring the therapeutic use of vitamin C as a potential epigenetic treatment for bladder cancer.
    Keywords Bladder cancer ; 5-Hydroxymethylcytosine ; Vitamin C ; TET ; Medicine ; R ; Genetics ; QH426-470
    Subject code 616
    Language English
    Publishing date 2018-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Growth Pattern of Clear Cell Renal Cell Carcinoma in Patients with Delayed Surgical Intervention

    Lei Zhang / Wenshi Yin / Lin Yao / Xuesong Li / Dong Fang / Da Ren / Zhongyuan Zhang / Yu Fan / Qun He / Weimin Ci / Zhisong He / Liqun Zhou

    BioMed Research International, Vol

    Fast Growth Rate Correlates with High Grade and May Result in Poor Prognosis

    2015  Volume 2015

    Abstract: Objectives. Previous studies revealed an unclear correlation between the growth rate of renal cell carcinoma (RCC) and tumor grade and did not focus on certain histological subtype. This report investigated the correlation between the growth rate and ... ...

    Abstract Objectives. Previous studies revealed an unclear correlation between the growth rate of renal cell carcinoma (RCC) and tumor grade and did not focus on certain histological subtype. This report investigated the correlation between the growth rate and tumor grade in clear cell RCC (ccRCC). Methods. We reviewed 60 patients with 61 ccRCC confirmed by delayed surgeries after at least 12 months of active surveillance. The linear growth rate (LGR), volumetric growth rate (VGR), and volume doubling time (VDT) were calculated, and their correlations with clinicopathologic characteristics were analyzed. Results. The mean LGR, VGR, and VDT were 0.86 (range 0–4.74) cm/year, 20.96 (range 0.31–211.93) cm3/year, and 667 (range 33–3321) days, respectively. ccRCCs with high grade had greater LGR (P<0.001) and VGR (P=0.001) and lower VDT (P=0.017) than ccRCCs with low grade. Grade (OR = 5.185, P=0.004) was the only independent risk factor of LGR >0.5 cm/year, and grade (OR = 3.006, P=0.046) and initial size (OR = 0.392, P=0.004) were independent risk factors of VDT <1 year. Five patients developed metastasis after surgery with LGR >0.5 cm/yr altogether; of them, four had cancer-related death by the last follow-up. Conclusions. Fast growth rate of ccRCC is significantly correlated with high tumor grade and may result in poor prognosis, especially for those with LGR >0.5 cm/yr.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: Programming and Inheritance of Parental DNA Methylomes in Mammals

    Wang, Lu / Jun Zhang / Jialei Duan / Xinxing Gao / Wei Zhu / Xingyu Lu / Lu Yang / Jing Zhang / Guoqiang Li / Weimin Ci / Wei Li / Qi Zhou / Neel Aluru / Fuchou Tang / Chuan He / Xingxu Huang / Jiang Liu

    Cell. 2014 May 08, v. 157

    2014  

    Abstract: The reprogramming of parental methylomes is essential for embryonic development. In mammals, paternal 5-methylcytosines (5mCs) have been proposed to be actively converted to oxidized bases. These paternal oxidized bases and maternal 5mCs are believed to ...

    Abstract The reprogramming of parental methylomes is essential for embryonic development. In mammals, paternal 5-methylcytosines (5mCs) have been proposed to be actively converted to oxidized bases. These paternal oxidized bases and maternal 5mCs are believed to be passively diluted by cell divisions. By generating single-base resolution, allele-specific DNA methylomes from mouse gametes, early embryos, and primordial germ cell (PGC), as well as single-base-resolution maps of oxidized cytosine bases for early embryos, we report the existence of 5hmC and 5fC in both maternal and paternal genomes and find that 5mC or its oxidized derivatives, at the majority of demethylated CpGs, are converted to unmodified cytosines independent of passive dilution from gametes to four-cell embryos. Therefore, we conclude that paternal methylome and at least a significant proportion of maternal methylome go through active demethylation during embryonic development. Additionally, all the known imprinting control regions (ICRs) were classified into germ-line or somatic ICRs.
    Keywords DNA ; cytosine ; embryogenesis ; genome ; germ cells ; mice
    Language English
    Dates of publication 2014-0508
    Size p. 979-991.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2014.04.017
    Database NAL-Catalogue (AGRICOLA)

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