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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: 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)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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