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Single Cell Spatial Transcriptomic Profiling Identifies a LINE1 Associated Disarrayed Immune Microenvironment in

Avril K Coley1, Chenyue Lu2,3, Amaya Pankaj2,3

  • 1Department of Surgery, Massachusetts General Hospital Harvard Medical School; Boston, MA, USA.

Biorxiv : the Preprint Server for Biology
|December 18, 2023
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Summary
This summary is machine-generated.

High expression of repeat RNAs like HERV-K and LINE1 correlates with poorer survival in hepatocellular carcinoma (HCC). These findings suggest repeat RNAs could be prognostic biomarkers and therapeutic targets for HCC.

Keywords:
LINE1Spatial transcriptomicshepatocellular carcinomaimmune microenvironmentrepeat RNAstumor microenvironment

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Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Dysregulation of viral-like repeat RNAs is common in malignancies and linked to immune responses.
  • Their role in hepatocellular carcinoma (HCC) and its immunological landscape remains understudied.

Purpose of the Study:

  • To investigate the expression of various repeat RNAs in HCC.
  • To analyze the relationship between repeat RNA expression, immune cell infiltration, and clinical outcomes in HCC.

Main Methods:

  • RNA in situ hybridization (RNA-ISH) for LINE1, HERV-K, HERV-H, and HSATII repeats.
  • Immunohistochemistry (IHC) for immune cell subpopulations and immune checkpoint markers.
  • Spatial transcriptomics on tumor and vessel regions.

Main Results:

  • High expression of HERV-K and LINE1 repeat RNAs was associated with worse overall survival in HCC patients.
  • LINE1 expression positively correlated with FOXP3 T-regulatory cells and TIM3 immune checkpoint expression.
  • Spatial transcriptomics revealed elevated expression of genes linked to epithelial-mesenchymal transition and proliferation in tumors with high HERV-K and LINE1 expression.

Conclusions:

  • Repeat RNAs show potential as prognostic biomarkers in HCC.
  • These repeat RNAs may represent novel therapeutic targets for HCC treatment.
  • Further research is necessary to elucidate the mechanisms by which repeat RNAs influence HCC tumorigenesis.