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Specific gene expression profiles are associated with a pathologic complete response to neoadjuvant therapy in esophageal adenocarcinoma

  • Patrick J. McLaren
  • , Anthony P. Barnes
  • , Willy Z. Terrell
  • , Gina M. Vaccaro
  • , Jack Wiedrick
  • , John G. Hunter
  • , James P. Dolan

Research output: Contribution to journalArticlepeer-review

Abstract

Background Predicting treatment response to chemo-radiotherapy (CRT) in esophageal cancer remains an unrealized goal despite studies linking constellations of genes to prognosis. We aimed to determine if specific expression profiles are associated with pathologic complete response (pCR) after neoadjuvant CRT. Methods Eleven genes previously associated with esophageal cancer prognosis were identified. Esophageal adenocarcinoma (EAC) patients treated with neoadjuvant CRT and esophagectomy were included. Patients were classified into two groups: pCR and no-or-incomplete response (NR). Polymerase chain reaction was used to evaluate gene expression. Omnibus testing was applied to overall gene expression differences between groups, and log-rank tests compared individual genes. Results Eleven pCR and eighteen NR patients were analyzed. Combined expression profiles were significantly different between pCR and NR groups (p < 0.01). The gene CCL28 was over-expressed in pCR patients (Log-HR: 1.53, 95%CI: 0.46–2.59, p = 0.005), and DKK3 was under-expressed in pCR (Log-HR: −1.03 95%CI: −1.97, −0.10, p = 0.031). Conclusion EAC tumors that demonstrated a pCR have genetic profiles that are significantly different from typical NR profiles. The genes CCL28 and DKK3 are potential predictors of treatment response.

Original languageEnglish (US)
Pages (from-to)915-920
Number of pages6
JournalAmerican journal of surgery
Volume213
Issue number5
DOIs
StatePublished - May 2017

Funding

This research was made possible by funding provided by the Michael J. Newton Esophageal Cancer Foundation (McLaren), the Oregon Clinical and Translational Research Institute (OCTRI), Knight Cancer Institute Clinical Scholar Award (Vaccaro) and a grant (no. UL1TR000128) from the National Center for Advancing Translational Sciences (NACATS) of the National Institutes of Health (Dolan). The authors would like to acknowledge the Oregon Health and Sciences Histopathology Shared Resource and Gene Profiling Shared Resource for their contributions to this study. No author has any financial conflict of interest to disclose. The first author, Dr. McLaren, and corresponding author, Dr. Dolan, had full access to all of the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis.

FundersFunder number
Knight Cancer Institute
Michael J. Newton Esophageal Cancer Foundation
Oregon Health and Sciences
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health
National Institute of Neurological Disorders and StrokeR01NS079433
National Center for Advancing Translational SciencesUL1TR000128
Oregon Clinical and Translational Research Institute

    Keywords

    • Biomarker
    • Esophageal cancer
    • Gene expression
    • Neoadjuvant therapy
    • Pathologic complete response

    ASJC Scopus subject areas

    • Surgery

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