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 language | English (US) |
|---|---|
| Pages (from-to) | 915-920 |
| Number of pages | 6 |
| Journal | American journal of surgery |
| Volume | 213 |
| Issue number | 5 |
| DOIs | |
| State | Published - 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.
| Funders | Funder 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 Stroke | R01NS079433 |
| National Center for Advancing Translational Sciences | UL1TR000128 |
| 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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