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Transcriptomic changes and gene fusions during the progression from Barrett's esophagus to esophageal adenocarcinoma.

Authors :
Fu Y
Agrawal S
Snyder DR
Yin S
Zhong N
Grunkemeyer JA
Dietz N
Corlett R
Hansen LA
Waddah AR
Nandipati KC
Xia J
Source :
Biomarker research [Biomark Res] 2024 Aug 07; Vol. 12 (1), pp. 78. Date of Electronic Publication: 2024 Aug 07.
Publication Year :
2024

Abstract

The incidence of esophageal adenocarcinoma (EAC) has surged by 600% in recent decades, with a dismal 5-year survival rate of just 15%. Barrett's esophagus (BE), affecting about 2% of the population, raises the risk of EAC by 40-fold. Despite this, the transcriptomic changes during the BE to EAC progression remain unclear. Our study addresses this gap through comprehensive transcriptomic profiling to identify key mRNA signatures and genomic alterations, such as gene fusions. We performed RNA-sequencing on BE and EAC tissues from 8 individuals, followed by differential gene expression, pathway and network analysis, and gene fusion prediction. We identified mRNA changes during the BE-to-EAC transition and validated our results with single-cell RNA-seq datasets. We observed upregulation of keratin family members in EAC and confirmed increased levels of keratin 14 (KRT14) using immunofluorescence. More differentiated BE marker genes are downregulated during progression to EAC, suggesting undifferentiated BE subpopulations contribute to EAC. We also identified several gene fusions absent in paired BE and normal esophagus but present in EAC. Our findings are critical for the BE-to-EAC transition and have the potential to promote early diagnosis, prevention, and improved treatment strategies for EAC.<br /> (© 2024. The Author(s).)

Details

Language :
English
ISSN :
2050-7771
Volume :
12
Issue :
1
Database :
MEDLINE
Journal :
Biomarker research
Publication Type :
Editorial & Opinion
Accession number :
39113153
Full Text :
https://doi.org/10.1186/s40364-024-00623-8