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. (2009) Gene expression analysis of diagnostic biopsies predicts pathological response to neoadjuvant chemoradiotherapy of esophageal cancer. Annals of Surgery, 250(5), pp. 729-736.

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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. Copyright © 2009 by Lippincott Williams & Wilkins.

Impact and interest:

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ID Code: 65224
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: antineoplastic agent, biological marker, cisplatin, fluorouracil, adult, aged, article, cancer adjuvant therapy, cancer patient, cancer staging, clinical article, cohort analysis, controlled study, diagnostic accuracy, esophagus biopsy, esophagus cancer, female, gene expression, human, human tissue, male, microarray analysis, molecular genetics, multiple cycle treatment, priority journal, quantitative analysis, reverse transcription polymerase chain reaction, RNA extraction, RNA hybridization, treatment outcome, treatment response, tumor cell, validation process, Antineoplastic Combined Chemotherapy Protocols, Biopsy, Esophageal Neoplasms, Gene Expression Profiling, Humans, Middle Aged, Neoadjuvant Therapy, Oligonucleotide Array Sequence Analysis
DOI: 10.1097/SLA.0b013e3181bce7e1
ISSN: 0003-4932
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2009 Lippincott Williams & Wilkins
Deposited On: 09 Dec 2013 04:34
Last Modified: 12 Mar 2014 23:27

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