ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2024
Comprehensive profiling of enhancer RNA in stage II/III colorectal cancer defines two prognostic subtypes with implications for immunotherapy.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 4 citations in OpenAlex.
- Decoding cancer heterogeneity through super-enhancer landscapes: from subtype discovery to therapeutic opportunity.Briefings in bioinformatics · 2025Review
- Enhancer RNAs profiling in colorectal cancer liver metastases reveals novel molecular subtypes with prognostic and therapeutic relevance.Discover oncology · 2025Article
- Enhancer RNA in cancer: identification, expression, resources, relationship with immunity, drugs, and prognosis.Briefings in functional genomics · 2025Review
- Impact of KRAS mutation on the tumor microenvironment in colorectal cancer.International journal of biological sciences · 2024Review
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6 authors at 2 institutions in 1 country.
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Abstract
backgroundRecently, enhancer RNAs (eRNAs) have garnered attention as pivotal biomarkers for the onset and progression of cancer. However, the landscape of eRNAs and the implications of eRNA-based molecular subtypes in stage II/III colorectal cancer (CRC) remain largely unexplored.
methodsComprehensive profiling of eRNAs was conducted on a public stage II/III CRC cohort with total RNA-seq data. We used unsupervised clustering of prognostic eRNAs to establish an eRNA-based subtyping system. Further evaluations included molecular characteristics, immune infiltration, clinical outcomes, and drug responses. Finally, we validated the eRNA-based subtyping system in The Cancer Genome Atlas (TCGA) CRC cohort.
resultsWe identified a total of 6453 expressed eRNAs, among which 237 were prognostic. A global upregulation of eRNAs was observed in microsatellite-stable (MSS) CRCs when compared to microsatellite instability-high (MSI-H) CRCs. Through consensus clustering, two novel molecular subtypes, termed Cluster 1(C1) and Cluster 2(C2), were further identified. C1, associated with the activation of epithelial-mesenchymal transition (EMT), hypoxia, and KRAS signaling pathways, showed poorer prognosis. C2, correlated with the canonical CRC subtype, exhibited superior survival outcomes. In addition, C1 showed enrichment with immune infiltration and more sensitivity to immune checkpoint inhibitors.
conclusionOur study unravels the molecular heterogeneity of stage II/III CRC at the eRNA level and highlights the potential applications of the novel eRNA-based subtyping system in predicting prognosis and guiding immunotherapy.
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