Decreased Expression of Gene Cluster at Chromosome 1q21 Defines Molecular Subgroups of Chemoradiotherapy Response in Esophageal Cancers

Purpose: Resistance to preoperative chemoradiotherapy (CTXRT) in 75% of patients with esophageal adenocarcinoma (EAC) underscores the need for identification of biomarkers of CTXRT response. We previously noted an association between decreased expression of epidermal differentiation complex (EDC) ge...

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Bibliographic Details
Published in:Clinical cancer research 2007-02, Vol.13 (3), p.912-919
Main Authors: LUTHRA, Madan G, AJANI, Jaffer A, IZZO, Julie, ENSOR, Joe, WU, Tsung-Teh, RASHID, Asif, LI ZHANG, PHAN, Alexandria, FUKAMI, Norio, LUTHRA, Rajyalakshmi
Format: Article
Language:English
Subjects:
Adenocarcinoma - drug therapy
Adenocarcinoma - genetics
Antineoplastic agents
Antineoplastic Agents - pharmacology
Biological and medical sciences
Biomarkers, Tumor
Chemoradiation Resistance
Chromosomes, Human, Pair 1
Cluster Analysis
Combined Modality Therapy
Disease Progression
Drug Resistance, Neoplasm
Epidermal Differentiation Complex
Esophageal Adenocarcinoma
Esophageal Neoplasms - drug therapy
Esophageal Neoplasms - genetics
Esophagus
Female
Gastroenterology. Liver. Pancreas. Abdomen
Gene Expression Regulation, Neoplastic
Humans
Male
Medical sciences
Molecular Subgroups
Multigene Family
Neoplasm Metastasis
Pathologic Complete Response
Pharmacology. Drug treatments
Polymerase Chain Reaction
Treatment Outcome
Tumors
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Summary:Purpose: Resistance to preoperative chemoradiotherapy (CTXRT) in 75% of patients with esophageal adenocarcinoma (EAC) underscores the need for identification of biomarkers of CTXRT response. We previously noted an association between decreased expression of epidermal differentiation complex (EDC) genes S100A2 and SPRR3 at chromosome 1q21 and CTXRT resistance. In the current study, we did an in-depth investigation of the expression of 1q21-1q25 region genes to uncover the role of the EDC and its flanking genes in CTXRT response. Experimental Design: We compared 19 pretreatment EAC specimens with normal squamous mucosa for the expression of 517 genes at chromosome 1q21-1q25 and selected target genes based on their differential expression. Using the pathologic complete-response (pathCR) status of the resected specimens as a representation of CTXRT sensitivity, we assessed the association between the expression of target genes and CTXRT response and clinical outcomes. Results: On the basis of the expression levels of IVL, CRNN, NICE-1, S100A2 , and SPPR3 , genes within and in close proximity to the EDC, cancers were segregated into high (subgroup I) or low (subgroup II) expressers. Four of the five pathCRs were high expressers. Thus, low expressers, with one exception, were all nonresponders. Patients in subgroup I also had longer survival than those in subgroup II, although this result was not statistically significant owing to the small study number. Conclusions: The expression levels of genes mapping within and close to the EDC define CTXRT response subgroups in EACs.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-06-1577