Dataset Information

A novel Chr1-miR-200 driven whole transcriptome signature shapes tumor immune microenvironment and predicts relapse in early-stage lung adenocarcinoma.

ABSTRACT:

Background

In Lung adenocarcinoma (LUAD), targeted therapies and immunotherapies have moved from metastatic to early stage and stratification of the relapse risk becomes mandatory. Here we identified a miR-200 based RNA signature that delineates Epithelial-to-mesenchymal transition (EMT) heterogeneity and predicts survival beyond current classification systems.

Methods

A miR-200 signature was identified using RNA sequencing. We scored the miR-200 signature by WISP (Weighted In Silico Pathology), used GSEA to identify pathway enrichments and MCP-counter to characterize immune cell infiltrates. We evaluate the clinical value of this signature in our series of LUAD and using TCGA and 7 published datasets.

Results

We identified 3 clusters based on supervised classification: I is miR-200-sign-down and enriched in TP53 mutations IIA and IIB are miR-200-sign-up: IIA is enriched in EGFR (p < 0.001), IIB is enriched in KRAS mutation (p < 0.001). WISP stratified patients into miR-200-sign-down (n = 65) and miR-200-sign-up (n = 42). Several biological processes were enriched in MiR-200-sign-down tumors, focal adhesion, actin cytoskeleton, cytokine/receptor interaction, TP53 signaling and cell cycle pathways. Fibroblast, immune cell infiltration and PDL1 expression were also significantly higher suggesting immune exhaustion. This signature stratified patients into high-vs low-risk groups, miR-200-sign-up had higher DFS, median not reached at 60 vs 41 months and within subpopulations with stage I, IA, IB, or II. Results were validated on TCGA data on 7 public datasets.

Conclusion

This EMT and miR-200-related prognostic signature refines prognosis evaluation independently of tumor stage and paves the way towards assessing the predictive value of this LUAD clustering to optimize perioperative treatment.

SUBMITTER: Garinet S

PROVIDER: S-EPMC10184345 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

A novel Chr1-miR-200 driven whole transcriptome signature shapes tumor immune microenvironment and predicts relapse in early-stage lung adenocarcinoma.

Garinet Simon S Didelot Audrey A Marisa Laetitia L Beinse Guillaume G Sroussi Marine M Le Pimpec-Barthes Françoise F Fabre Elizabeth E Gibault Laure L Laurent-Puig Pierre P Mouillet-Richard Sophie S Legras Antoine A Blons Hélène H

Journal of translational medicine 20230515 1

<h4>Background</h4>In Lung adenocarcinoma (LUAD), targeted therapies and immunotherapies have moved from metastatic to early stage and stratification of the relapse risk becomes mandatory. Here we identified a miR-200 based RNA signature that delineates Epithelial-to-mesenchymal transition (EMT) heterogeneity and predicts survival beyond current classification systems.<h4>Methods</h4>A miR-200 signature was identified using RNA sequencing. We scored the miR-200 signature by WISP (Weighted In Sil ...[more]

PMID: 37189151

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Dataset Information

A novel Chr1-miR-200 driven whole transcriptome signature shapes tumor immune microenvironment and predicts relapse in early-stage lung adenocarcinoma.

Background

Methods

Results

Conclusion

Publications

A novel Chr1-miR-200 driven whole transcriptome signature shapes tumor immune microenvironment and predicts relapse in early-stage lung adenocarcinoma.

Similar Datasets

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