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
Article
in English
| IBECS
| ID: ibc-VR-52
Responsible library:
ES1.1
Localization: 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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Full text:
Available
Collection:
National databases
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Spain
Health context:
Sustainable Health Agenda for the Americas
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SDG3 - Health and Well-Being
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Neglected Diseases
Health problem:
Goal 9: Noncommunicable diseases and mental health
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Goal 10: Communicable diseases
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Target 3.3: End transmission of communicable diseases
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Neglected Diseases
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Zoonoses
Database:
IBECS
Main subject:
Prognosis
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Child Nutrition
/
Palliative Care
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Patents as Topic
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Patients
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Physical Education and Training
/
Pruritus
/
Schools
/
Autistic Disorder
/
Sports
Type of study:
Controlled clinical trial
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Etiology study
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Incidence study
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Observational study
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Prognostic study
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Qualitative research
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Risk factors
Limits:
Humans
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Female
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Male
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Child
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Aged
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Adolescent
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Child, preschool
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Infant
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Infant, Newborn
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Pregnancy
Country/Region as subject:
Europa
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South America
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Asia
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Chile
Language:
Spanish
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English
Journal:
An. pediatr. (2003. Ed. impr.)
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Asclepio
/
Clin. transl. oncol. (Print)
/
Enferm. intensiva (Ed. impr.)
/
Gastroenterol. hepatol. (Ed. impr.)
/
Int. microbiol
/
Med. oral patol. oral cir. bucal (Internet)
/
Nutr. clín. diet. hosp
/
Nutr. hosp
/
Reumatol. clín. (Barc.)
Year:
2022
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2023
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2021
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2024
Document type:
Article
Institution/Affiliation country:
Acibadem University/Turkey
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Complejo Asistencial de Segovia/España
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European University of Lefke/Turkey
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Guizhou Medical University/China
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Hospital Clinic of Barcelona/Spain
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Hospital Clinic/Spain
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Hospital Comarcal de Manacor/España
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Hospital Son Llatzer/España
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Hospital Universitari Arnau de Vilanova/España
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Hospital Universitari Son Espases/España