ArticleDiscover oncology2025
Enhancer RNAs profiling in colorectal cancer liver metastases reveals novel molecular subtypes with prognostic and therapeutic relevance.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundEnhancer RNAs (eRNAs) are essential for cancer initiation and progression. However, the landscape of eRNAs and the clinical significance of eRNAs in colorectal cancer (CRC) liver metastases (CRLM) remain largely unknown.
methodsWe comprehensively profiled eRNAs in a CRLM cohort and delineated eRNA-based CRLM subtypes through unsupervised clustering of eRNAs and validated the subtyping framework in an external cohort. Molecular characteristics, immune infiltration, prognostic outcomes, and chemotherapy responses of the novel CRLM subtypes were further explored. Finally, we explored chemoresistance-related eRNAs and tentatively investigated the roles of eRNAs in CRC oxaliplatin resistance in vitro.
resultsThree novel eRNA-based CRLM subtypes, known as C1, C2, and C3, have been identified and validated in an external cohort. C1 has transcriptomic features of proliferative pathways. C2 is associated with the canonical primary CRC subtype. C3 is active in immune pathways and metabolic pathways. C2 has the highest chemotherapy response rate and has a better survival outcome than C1 and C3. In addition, we have revealed that knockdown of the eRNA (chr7:130571851-130572495) might influence oxaliplatin sensitivity in CRC cells.
conclusionsOur findings unveil the molecular heterogeneity of CRLM through the lens of eRNAs and underscore the potential utility of eRNA in stratifying CRLM and guiding precision therapy.
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