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

Authors' Affiliations: Departments of ¹ Pathology, ² Gastrointestinal Medical Oncology, ³ Experimental Therapeutics, ⁴ Biostatistics and Applied Math, ⁵ Gastrointestinal Medicine and Nutrition, and ⁶ Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Rajyalakshmi Luthra, Division of Pathology and Laboratory Medicine, University of Texas M. D. Anderson Cancer Center, 8515 Fannin St., NAO1.091, Houston, TX 77054. Phone: 713-794-5443; Fax: 713-794-4773; E-mail: rluthra{at}mdanderson.org.

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.