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Gene expression analysis of diagnostic biopsies predicts pathological response to neoadjuvant chemoradiotherapy of esophageal cancer

Maher, Stephen G.; Gillham, Charles M.; Duggan, Shane P.; Smyth, Paul C.; Miller, Nicola; Muldoon, Cian; O'Byrne, Kenneth J.; Sheils, Orla M.; Hollywood, Donal; Reynolds, John V.

Authors

Stephen G. Maher

Charles M. Gillham

Shane P. Duggan

Paul C. Smyth

Nicola Miller

Cian Muldoon

Kenneth J. O'Byrne

Orla M. Sheils

Donal Hollywood

John V. Reynolds



Abstract

OBJECTIVE:This study explored gene expression differences in predicting response to chemoradiotherapy in esophageal cancer. PURPOSE:A major pathological response to neoadjuvant chemoradiation is observed in about 40% of esophageal cancer patients and is associated with favorable outcomes. However, patients with tumors of similar histology, differentiation, and stage can have vastly different responses to the same neoadjuvant therapy. This dichotomy may be due to differences in the molecular genetic environment of the tumor cells. BACKGROUND DATA:Diagnostic biopsies were obtained from a training cohort of esophageal cancer patients (13), and extracted RNA was hybridized to genome expression microarrays. The resulting gene expression data was verified by qRT-PCR. In a larger, independent validation cohort (27), we examined differential gene expression by qRT-PCR. The ability of differentially-regulated genes to predict response to therapy was assessed in a multivariate leave-one-out cross-validation model. RESULTS:Although 411 genes were differentially expressed between normal and tumor tissue, only 103 genes were altered between responder and non-responder tumor; and 67 genes differentially expressed >2-fold. These included genes previously reported in esophageal cancer and a number of novel genes. In the validation cohort, 8 of 12 selected genes were significantly different between the response groups. In the predictive model, 5 of 8 genes could predict response to therapy with 95% accuracy in a subset (74%) of patients. CONCLUSIONS:This study has identified a gene microarray pattern and a set of genes associated with response to neoadjuvant chemoradiation in esophageal cancer. The potential of these genes as biomarkers of response to treatment warrants further investigation.

Citation

Maher, S. G., Gillham, C. M., Duggan, S. P., Smyth, P. C., Miller, N., Muldoon, C., …Reynolds, J. V. (2009). Gene expression analysis of diagnostic biopsies predicts pathological response to neoadjuvant chemoradiotherapy of esophageal cancer. Annals of Surgery, 250(5), 729-737. doi:10.1097/SLA.0b013e3181bce7e1

Journal Article Type Article
Publication Date Nov 1, 2009
Deposit Date Nov 13, 2014
Journal Annals Of Surgery
Print ISSN 0003-4932
Electronic ISSN 1528-1140
Publisher Lippincott, Williams & Wilkins
Peer Reviewed Peer Reviewed
Volume 250
Issue 5
Pages 729-737
DOI https://doi.org/10.1097/SLA.0b013e3181bce7e1
Keywords Surgery
Public URL https://hull-repository.worktribe.com/output/467876
Publisher URL https://journals.lww.com/annalsofsurgery/Abstract/2009/11000/Gene_Expression_Analysis_of_Diagnostic_Biopsies.10.aspx