Decreased expression of gene cluster at chromosome 1q21 defines molecular subgroups of chemoradiotherapy response in esophageal cancers

Madan G. Luthra, Jaffer A. Ajani, Julie Izzo, Joe Ensor, Tsung Teh Wu, Asif Rashid, Li Zhang, Alexandria Phan, Norio Fukami, Rajyalakshmi Luthra

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)912-919
Number of pages8
JournalClinical Cancer Research
Volume13
Issue number3
DOIs
StatePublished - Feb 1 2007
Externally publishedYes

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Chemoradiotherapy
Esophageal Neoplasms
Multigene Family
Chromosomes
Genes
Adenocarcinoma
Gene Expression
Chromosome Mapping
Mucous Membrane
Research Design
Biomarkers
Survival
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Decreased expression of gene cluster at chromosome 1q21 defines molecular subgroups of chemoradiotherapy response in esophageal cancers. / Luthra, Madan G.; Ajani, Jaffer A.; Izzo, Julie; Ensor, Joe; Wu, Tsung Teh; Rashid, Asif; Zhang, Li; Phan, Alexandria; Fukami, Norio; Luthra, Rajyalakshmi.

In: Clinical Cancer Research, Vol. 13, No. 3, 01.02.2007, p. 912-919.

Research output: Contribution to journalArticle

Luthra, Madan G. ; Ajani, Jaffer A. ; Izzo, Julie ; Ensor, Joe ; Wu, Tsung Teh ; Rashid, Asif ; Zhang, Li ; Phan, Alexandria ; Fukami, Norio ; Luthra, Rajyalakshmi. / Decreased expression of gene cluster at chromosome 1q21 defines molecular subgroups of chemoradiotherapy response in esophageal cancers. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 3. pp. 912-919.
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abstract = "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.",
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AU - Luthra, Madan G.

AU - Ajani, Jaffer A.

AU - Izzo, Julie

AU - Ensor, Joe

AU - Wu, Tsung Teh

AU - Rashid, Asif

AU - Zhang, Li

AU - Phan, Alexandria

AU - Fukami, Norio

AU - Luthra, Rajyalakshmi

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N2 - 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.

AB - 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.

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