Comprehensive profiling of enhancer RNA in stage II/III colorectal cancer defines two prognostic subtypes with implications for immunotherapy / El perfil completo del ARN potenciador en el cáncer colorrectal en estadio II/III define dos subtipos de pronóstico con implicaciones para la inmunoterapia
Clin. transl. oncol. (Print)
; 26(4): 891-904, Abr. 2024. ilus
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em En
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| ID: ibc-VR-52
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ES1.1
Localização: ES15.1 - BNCS
ABSTRACT
Background: Recently, 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. Methods: Comprehensive 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. Results: We 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 epithelialmesenchymal 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. Conclusion: Our 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.(AU)
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Base de dados:
IBECS
Métodos Terapêuticos e Terapias MTCI:
Terapias_biologicas
/
Trofoterapia
Assunto principal:
Prognóstico
/
Nutrição da Criança
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Cuidados Paliativos
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Patentes como Assunto
/
Pacientes
/
Educação Física e Treinamento
/
Prurido
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Instituições Acadêmicas
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Transtorno Autístico
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Esportes
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Qualitative_research
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Risk_factors_studies
País/Região como assunto:
Europa
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America do sul
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Asia
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Chile
Idioma:
Es
/
En
Revista:
An. pediatr. (2003. Ed. impr.)
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Asclepio
/
Clin. transl. oncol. (Print)
/
Enferm. intensiva (Ed. impr.)
/
Gastroenterol. hepatol. (Ed. impr.)
/
Int. microbiol
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Med. oral patol. oral cir. bucal (Internet)
/
Nutr. clín. diet. hosp
/
Nutr. hosp
/
Reumatol. clín. (Barc.)
Ano de publicação:
2022
/
2023
/
2021
/
2024
Tipo de documento:
Article