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

• 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
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-06-1577

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.