Integrative Single-Cell Analysis Reveals Transcriptional and Epigenetic Regulatory Features of Clear Cell Renal Cell Carcinoma

Yu, Zhenyuan; Lv, Yufang; Su, Cheng; Lu, Wenhao; Zhang, RuiRui; Li, Jiaping; Guo, Bingqian; Yan, Haibiao; Liu, Deyun; Yang, Zhanbin; Mi, Hua; Mo, Linjian; Guo, Yi; Feng, Wenyu; Xu, Haotian; Peng, Wenyi; Cheng, Jian; Nan, Aruo; Mo, Zengnan

doi:10.1158/0008-5472.can-22-2224

Cited by 33 publications

(21 citation statements)

References 68 publications

(153 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous bulk RNA-seq based transcriptome analyses of ccRCC multi-patient samples focused mostly on prognostic gene screening and clinical outcome prediction, with less consideration given to intercellular heterogeneity (STable 1). Meanwhile, scRNA-seq of ccRCC focuses on the research of cell origin 53 , identi cation and function of new cell groups 54,55 and the heterogeneity of tumor cells 24 .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of RNA sequencing and integrated machine learning reveals a metabolism related prognostic signature for improving outcomes in ccRCC

Liu,

Yan

et al. 2024

Preprint

View full text Add to dashboard Cite

The connection between metabolic reprogramming and tumor progression has been demonstrated in an increasing number of researches. However, further research is required to identify how metabolic reprogramming affects interpatient heterogeneity and prognosis in clear cell renal cell carcinoma (ccRCC). In this work, Single-cell RNA sequencing (scRNA-seq) based deconvolution was utilized to create a malignant cell hierarchy with metabolic differences and to investigate the relationship between metabolic biomarkers and prognosis. Simultaneously, we created a machine learning-based approach for creating metabolism related prognostic signature (MRPS). Following the administration of immune checkpoint inhibitors (ICIs), MRPS shows consistent and strong performance and is an independent risk factor for overall survival. Furthermore, compared to 51 published signatures and conventional clinical features, MRPS showed substantially higher accuracy. GGT6, an essential metabolic indicator and component of MRPS, has been proven to support proliferation and invasion in ccRCC. In conclusion, MRPS has the potential to be a highly effective tool in improving the clinical results of patients with ccRCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of RNA sequencing and integrated machine learning reveals a metabolism related prognostic signature for improving outcomes in ccRCC

Liu,

Yan

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…This suggests that although WT1 may exhibit similar expression levels, the accessibility of the regulatory elements of WT1 or WT1 interaction with transcription factors may signi cantly vary between DCM and control groups. Several studies have attempted to integrate scRNA-seq and scATAC data to gain a holistic understanding of gene regulation and cellular behavior in pathological conditions [10,11].…”

Section: Discussionmentioning

confidence: 99%

Regulatory and Communication Shifts in Dilated Cardiomyopathy: A Multimodal Single-Cell Analysis

Tang#,

Zhang#,

Xu#

et al. 2024

Preprint

View full text Add to dashboard Cite

Dilated cardiomyopathy (DCM), a major cause of heart failure in young adults, is characterized by ventricular dilation and progressive heart muscle dysfunction. Cellular mechanisms driving DCM have not been elucidated despite advances in genomic medicine. This study performed comprehensive multimodal single-cell analysis integrating RNA sequencing, assay for transposase-accessible chromatin with sequencing, and spatial transcriptomics data of cardiac tissues from patients with DCM and control subjects. The complex cellular heterogeneity and a novel neuro-cardiac interface were identified in DCM. The neuronal signaling pathways, including GABA receptor signaling and WT1 transcription factor activity, were profoundly dysregulated in the cardiomyocytes of patients with DCM. Cell-cell signaling analysis revealed that the communication patterns were altered, especially the upregulation of IGF and NRG signaling, suggesting a redefined role of adipocytes and lymphatic cells in DCM pathogenesis. The results of neuronal marker immunostaining analysis were consistent with those of bioinformatics analysis and indicated a potential cross-talk between cardiomyocytes and neurons. The findings of this study provided novel insights into the molecular mechanisms of DCM and identified potential therapeutic targets for DCM, which will enable the development of precision therapeutic approaches for cardiomyopathies.

show abstract

“…The incidence of renal cell carcinoma has been increasing over the past several decades, and its most common histologic subtype is clear cell carcinoma [ 19 ]. Finding new useful biomarkers to direct individualized treatment of KIRC and predict patient prognosis is crucial due to the high mortality rate that KIRC exhibits.…”

Section: Discussionmentioning

confidence: 99%

Elevated ADH5 expression suggested better prognosis in kidney renal clear cell carcinoma (KIRC) and related to immunity through single-cell and bulk RNA-sequencing

Sun,

Zhang,

et al. 2024

BMC Urol

View full text Add to dashboard Cite

Background Despite the rapid advances in modern medical technology, kidney renal clear cell carcinoma (KIRC) remains a challenging clinical problem in urology. Researchers urgently search for useful markers to break through the therapeutic conundrum due to its high lethality. Therefore, the study explores the value of ADH5 on overall survival (OS) and the immunology of KIRC. Methods The gene expression matrix and clinical information on ADH5 in the TCGA database were validated using external databases and qRT-PCR. To confirm the correlation between ADH5 and KIRC prognosis, univariate/multivariate Cox regression analysis was used. We also explored the signaling pathways associated with ADH5 in KIRC and investigated its association with immunity. Results The mRNA and protein levels showed an apparent downregulation of ADH5 in KIRC. Correlation analysis revealed that ADH5 was directly related to histological grade, clinical stage, and TMN stage (p < 0.05). Univariate and multivariate Cox regression analysis identified ADH5 as an independent factor affecting the prognosis of KIRC. Enrichment analysis looked into five ADH5-related signaling pathways. The results showed no correlation between ADH5 and TMB, TNB, and MSI. From an immunological perspective, ADH5 was found to be associated with the tumor microenvironment, immune cell infiltration, and immune checkpoints. Lower ADH5 expression was associated with greater responsiveness to immunotherapy. Single-cell sequencing revealed that ADH5 is highly expressed in immune cells. Conclusion ADH5 could be a promising prognostic biomarker and a potential therapeutic target for KIRC. Besides, it was found that KIRC patients with low ADH5 expression were more sensitive to immunotherapy.

show abstract

Integrative Single-Cell Analysis Reveals Transcriptional and Epigenetic Regulatory Features of Clear Cell Renal Cell Carcinoma

Cited by 33 publications

References 68 publications

Comprehensive analysis of RNA sequencing and integrated machine learning reveals a metabolism related prognostic signature for improving outcomes in ccRCC

Comprehensive analysis of RNA sequencing and integrated machine learning reveals a metabolism related prognostic signature for improving outcomes in ccRCC

Regulatory and Communication Shifts in Dilated Cardiomyopathy: A Multimodal Single-Cell Analysis

Elevated ADH5 expression suggested better prognosis in kidney renal clear cell carcinoma (KIRC) and related to immunity through single-cell and bulk RNA-sequencing

Contact Info

Product

Resources

About