10.6084/M9.FIGSHARE.C.6299925.V1
Hirsch Matani
Hirsch
Matani
Allegheny Health Network
Divya Sahu
Divya
Sahu
City Of Hope National Medical Center
Michael Paskewicz
Michael
Paskewicz
Allegheny Health Network
Anastasia Gorbunova
Anastasia
Gorbunova
Allegheny Health Network
Ashten N. Omstead
Ashten N.
Omstead
Allegheny Health Network
Rodney Wegner
Rodney
Wegner
Allegheny Health Network
Gene G. Finley
Gene G.
Finley
Allegheny Health Network
Blair A. Jobe
Blair A.
Jobe
Allegheny Health Network
Ronan J. Kelly
Ronan J.
Kelly
Baylor University Medical Center
Ali H. Zaidi
Ali H.
Zaidi
Allegheny Health Network
Ajay Goel
Ajay
Goel
City Of Hope National Medical Center
Baylor University Medical Center
Baylor Scott & White Health
Prognostic and predictive biomarkers for response to neoadjuvant chemoradiation in esophageal adenocarcinoma
Abstract Background Esophageal adenocarcinoma is a lethal disease. For locally advanced patients, neoadjuvant chemoradiotherapy followed by surgery is the standard of care. Risk stratification relies heavily on clinicopathologic features, particularly pathologic response, which is inadequate, therefore establishing the need for new and reliable biomarkers for risk stratification. Methods Thirty four patients with locally advanced esophageal adenocarcinoma were analyzed, of which 21 received a CROSS regimen with carboplatin, paclitaxel, and radiation. Capture-based targeted sequencing was performed on the paired baseline and post-treatment samples. Differentially mutated gene analysis between responders and non-responders of treatment was performed to determine predictors of response. A univariate Cox proportional hazard regression was used to examine associations between gene mutation status and overall survival. Results A 3-gene signature, based on mutations in EPHA5, BCL6, and ERBB2, was identified that robustly predicts response to the CROSS regimen. For this model, sensitivity was 84.6% and specificity was 100%. Independently, a 9 gene signature was created using APC, MAP3K6, ETS1, CSF3R, PDGFRB, GATA2, ARID1A, PML, and FGF6, which significantly stratifies patients into risk categories, prognosticating for improved relapse-free (pā=ā4.73E-03) and overall survival (pā=ā3.325E-06). The sensitivity for this model was 73.33% and the specificity was 94.74%. Conclusion We have identified a 3-gene signature (EPHA5, BCL6, and ERBB2) that is predictive of response to neoadjuvant chemoradiotherapy and a separate prognostic 9-gene classifier that predicts survival outcomes. These panels provide significant potential for personalized management of locally advanced esophageal cancer.
Medicine
Cell Biology
Genetics
Molecular Biology
Immunology
69999 Biological Sciences not elsewhere classified
19999 Mathematical Sciences not elsewhere classified
Cancer
figshare
2022
2022-11-15
2022-11-15
Collection
10.1186/s40364-022-00429-6
10.6084/m9.figshare.c.6299925
CC BY 4.0