Single‐cell transcriptomic analysis deciphers key transitional signatures associated with oncogenic evolution in human intramucosal oesophageal squamous cell carcinoma

Liu, Xin‐Yang; Liu, Yan‐Bo; Xu, Jiacheng; Zhang, Yifei; Ruan, Yuanyuan; Zhao, Yi; Wu, Lin‐Feng; Hu, Jianwei; Zhang, Zhen; He, Meng‐Jiang; Chen, Tian‐Yin; Xu, Xiao-Yue; Zhang, Jing‐Wei; Zhang, Yi‐Qun; Zhou, Ping‐Hong

doi:10.1002/ctm2.1203

Cited by 11 publications

(9 citation statements)

References 50 publications

(105 reference statements)

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“…By contrast, the immune system faces possible collapse due to the tumor invasion. 45 The CD4+ T lymphocyte number usually decreases significantly. Therefore, immune monitoring for cancer patients can provide important indications for cancer treatment planning and prognosis.…”

Section: Resultsmentioning

confidence: 99%

DNA framework signal amplification platform-based high-throughput systemic immune monitoring

Chen,

Zhang

et al. 2024

Sig Transduct Target Ther

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Systemic immune monitoring is a crucial clinical tool for disease early diagnosis, prognosis and treatment planning by quantitative analysis of immune cells. However, conventional immune monitoring using flow cytometry faces huge challenges in large-scale sample testing, especially in mass health screenings, because of time-consuming, technical-sensitive and high-cost features. However, the lack of high-performance detection platforms hinders the development of high-throughput immune monitoring technology. To address this bottleneck, we constructed a generally applicable DNA framework signal amplification platform (DSAP) based on post-systematic evolution of ligands by exponential enrichment and DNA tetrahedral framework-structured probe design to achieve high-sensitive detection for diverse immune cells, including CD4+, CD8+ T-lymphocytes, and monocytes (down to 1/100 μl). Based on this advanced detection platform, we present a novel high-throughput immune-cell phenotyping system, DSAP, achieving 30-min one-step immune-cell phenotyping without cell washing and subset analysis and showing comparable accuracy with flow cytometry while significantly reducing detection time and cost. As a proof-of-concept, DSAP demonstrates excellent diagnostic accuracy in immunodeficiency staging for 107 HIV patients (AUC > 0.97) within 30 min, which can be applied in HIV infection monitoring and screening. Therefore, we initially introduced promising DSAP to achieve high-throughput immune monitoring and open robust routes for point-of-care device development.

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Section: Resultsmentioning

confidence: 99%

DNA framework signal amplification platform-based high-throughput systemic immune monitoring

Chen,

Zhang

et al. 2024

Sig Transduct Target Ther

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“…We identified TREM2 Macro as a critical mediator of tumor progression through MDK-related communications, especially the MDK-NCL axis. Other studies have indicated that tumor cells confer a malignant phenotype to other cells through the MDK-NCL axis and alter the TME to promote angiogenesis and cancer metastasis 27–29 . This suggests that malignant cells directly recruit TREM2+ macrophages to the TME, contributing to a more aggressive tumor phenotype.…”

Section: Discussionmentioning

confidence: 98%

“…Other studies have indicated that tumor cells confer a malignant phenotype to other cells through the MDK-NCL axis and alter the TME to promote angiogenesis and cancer metastasis. [27][28][29] This suggests that malignant cells directly recruit TREM2+ macrophages to the TME, contributing to a more aggressive tumor phenotype. Therefore, targeting the MDK-NCL axis emerges as a promising therapeutic avenue.…”

Section: Discussionmentioning

confidence: 99%

Single-cell dissection of the multicellular ecosystem and molecular features underlying microvascular invasion in HCC

Li,

Zhang,

Wen

et al. 2023

Hepatology

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Background and aims: Microvascular invasion (MVI) is a crucial pathological hallmark of hepatocellular carcinoma (HCC), intricately associated with poor outcomes, early recurrence and intrahepatic metastasis following surgical resection and transplantation. However, the intricate tumor microenvironment (TME) and transcriptional programs underlying MVI in HCC remain poorly understood. Approach and results: We performed single-cell RNA sequencing of 46,789 individual cells from 10 samples of MVI+ (MVI present) and MVI- (MVI absent) HCC patients. We conducted comprehensive and comparative analyses to characterize cellular and molecular features associated with MVI, and validated key findings using external bulk, single-cell and spatial transcriptomic datasets, coupled with multiplex immunofluorescence assays. The comparison identified specific subtypes of immune and stromal cells critical to the formation of the immunosuppressive and pro-metastatic microenvironment in MVI+ tumors, including cycling T cells, LAMP3+ dendritic cells, TREM2+ macrophages, myofibroblasts, and arterial i endothelial cells. MVI+ malignant cells are characterized by high proliferation rates while MVI-malignant cells exhibit an inflammatory milieu. Additionally, we identified the MDK-dominated interaction between TREM2+ macrophages and malignant cells as a contributor to MVI formation and tumor progression. Notably, we unveiled a spatially co-located multicellular community exerting a dominant role in shaping the immunosuppressive microenvironment of MVI and correlating with unfavorable prognosis. Conclusions: This study provides a comprehensive single-cell atlas of MVI in HCC, shedding light on the complex multicellular ecosystem and molecular features associated with MVI. These findings deepen our understanding of the underlying mechanisms driving MVI and provide valuable insights for improving clinical diagnosis and developing more effective treatment strategies.

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“…Additionally, the MIF/CXCR4 pathway is considered crucial for the recruitment of mesenchymal stem cells 47 . Single-cell transcriptomic studies have demonstrated that tumor cells can also affect CAFs 48 and endothelial cells 49 through the MDK-NCL pathway, contributing to an immunosuppressive microenvironment. Signaling pathways associated with stemness play a significant role in systemic treatment resistance 50 .…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA-Seq Elucidates the Crosstalk Between Cancer Stem Cells and the Tumor Microenvironment in Hepatocellular Carcinoma

Lin,

Li,

Yang

et al. 2024

J. Cancer

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Background: The challenge of systemic treatment for hepatocellular carcinoma (HCC) stems from the development of drug resistance, primarily driven by the interplay between cancer stem cells (CSCs) and the tumor microenvironment (TME). However, there is a notable dearth of comprehensive research investigating the crosstalk between CSCs and stromal cells or immune cells within the TME of HCC. Methods: We procured single-cell RNA sequencing (scRNA-Seq) data from 16 patients diagnosed with HCC. Employing meticulous data quality control and cell annotation procedures, we delineated distinct CSCs subtypes and performed multi-omics analyses encompassing metabolic activity, cell communication, and cell trajectory. These analyses shed light on the potential molecular mechanisms governing the interaction between CSCs and the TME, while also identifying CSCs' developmental genes. By combining these developmental genes, we employed machine learning algorithms and RT-qPCR to construct and validate a prognostic risk model for HCC. Results: We successfully identified CSCs subtypes residing within malignant cells. Through meticulous enrichment analysis and assessment of metabolic activity, we discovered anomalous metabolic patterns within the CSCs microenvironment, including hypoxia and glucose deprivation. Moreover, CSCs exhibited aberrant activity in signaling pathways associated with lipid metabolism. Furthermore, our investigations into cell communication unveiled that CSCs possess the capacity to modulate stromal cells and immune cells through the secretion of MIF or MDK, consequently exerting regulatory control over the TME. Finally, through cell trajectory analysis, we found developmental genes of CSCs. Leveraging these genes, we successfully developed and validated a prognostic risk model (APCS, ADH4, FTH1, and HSPB1) with machine learning and RT-qPCR. Conclusions: By means of single-cell multi-omics analysis, this study offers valuable insights into the potential molecular mechanisms governing the interaction between CSCs and the TME, elucidating the pivotal role CSCs play within the TME. Additionally, we have successfully established a comprehensive clinical prognostic model through bulk RNA-Seq data.

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Single‐cell transcriptomic analysis deciphers key transitional signatures associated with oncogenic evolution in human intramucosal oesophageal squamous cell carcinoma

Cited by 11 publications

References 50 publications

DNA framework signal amplification platform-based high-throughput systemic immune monitoring

DNA framework signal amplification platform-based high-throughput systemic immune monitoring

Single-cell dissection of the multicellular ecosystem and molecular features underlying microvascular invasion in HCC

Single-cell RNA-Seq Elucidates the Crosstalk Between Cancer Stem Cells and the Tumor Microenvironment in Hepatocellular Carcinoma

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