Dataset Information

Dysregulated Repeat Element Viral-like Immune Response in Hepatocellular Carcinoma.

ABSTRACT:

Purpose

Dysregulation of viral-like repeat RNAs are a common feature across many malignancies that are linked with immunological response, but the characterization of these in hepatocellular carcinoma (HCC) is understudied. In this study, we performed RNA in situ hybridization (RNA-ISH) of different repeat RNAs, immunohistochemistry (IHC) for immune cell subpopulations, and spatial transcriptomics to understand the relationship of HCC repeat expression, immune response, and clinical outcomes.

Experimental design

RNA-ISH for LINE1, HERV-K, HERV-H, and HSATII repeats and IHC for T-cell, Treg, B-cell, macrophage, and immune checkpoint markers were performed on 43 resected HCC specimens. Spatial transcriptomics on tumor and vessel regions of interest was performed on 28 specimens from the same cohort.

Results

High HERV-K and high LINE1 expression were both associated with worse overall survival. There was a positive correlation between LINE1 expression and FOXP3 T-regulatory cells (r = 0.51 p < 0.001) as well as expression of the TIM3 immune checkpoint (r = 0.34, p = 0.03). Spatial transcriptomic profiling of HERV-K high and LINE-1 high tumors identified elevated expression of multiple genes previously associated with epithelial mesenchymal transition, cellular proliferation, and worse overall prognosis in HCC including SSX1, MAGEC2, and SPINK1.

Conclusion

Repeat RNAs may serve as useful prognostic biomarkers in HCC and may also serve as novel therapeutic targets. Additional study is needed to understand the mechanisms by which repeat RNAs impact HCC tumorigenesis.

SUBMITTER: Coley AK

PROVIDER: S-EPMC10723373 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Coley Avril K AK Nawrocki Cole C Patel Bidish K BK Pankaj Amaya A Guo Zhoubo Z Emmett Matthew J MJ Lang Evan R ER Song Yuhui Y Xu Katherine H KH Ferrone Cristina R CR Deshpande Vikram V Nieman Linda T LT Aryee Martin J MJ Franses Joseph W JW Ting David T DT

bioRxiv : the preprint server for biology 20250526

<h4>Purpose</h4>Hepatocellular carcinoma (HCC) is a lethal malignancy driven by complex interactions between cancer cells, immune cells, and additional stromal cells in the tumor microenvironment (TME). The LINE1 retrotransposon is a ubiquitous repeat RNA whose de-repression leads to significant cancer cell-intrinsic and TME changes that promote aggressive tumor characteristics. We leveraged single cell spatial transcriptomic profiling to characterize the relationship between LINE1 and differenc ...[more]

PMID: 38105940

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