Patrick J McLaren1, Anthony P Barnes2, Willy Z Terrell1, Gina M Vaccaro3, Jack Wiedrick4, John G Hunter1, James P Dolan5. 1. Department of Surgery, Division of Gastrointestinal and General Surgery, Oregon Health and Science University, Portland, OR, USA. 2. Knight Cardiovascular Institute, Department of Medicine, Oregon Health & Science University, Portland, OR, USA. 3. Department of Medicine, Division of Medical Oncology, Oregon Health and Science University, Portland, OR, USA. 4. School of Public Health, Division of Biostatistics, Oregon Health and Science University, Portland, OR, USA. 5. Department of Surgery, Division of Gastrointestinal and General Surgery, Oregon Health and Science University, Portland, OR, USA. Electronic address: dolanj@ohsu.edu.
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.
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.
Authors: Stephen H Bailey; David A Bull; David H Harpole; Jeffrey J Rentz; Leigh A Neumayer; Theodore N Pappas; Jennifer Daley; William G Henderson; Barbara Krasnicka; Shukri F Khuri Journal: Ann Thorac Surg Date: 2003-01 Impact factor: 4.330
Authors: Soonmyung Paik; Gong Tang; Steven Shak; Chungyeul Kim; Joffre Baker; Wanseop Kim; Maureen Cronin; Frederick L Baehner; Drew Watson; John Bryant; Joseph P Costantino; Charles E Geyer; D Lawrence Wickerham; Norman Wolmark Journal: J Clin Oncol Date: 2006-05-23 Impact factor: 44.544
Authors: Christopher J Peters; Jonathan R E Rees; Richard H Hardwick; James S Hardwick; Sarah L Vowler; Chin-Ann J Ong; Chunsheng Zhang; Vicki Save; Maria O'Donovan; Doris Rassl; Derek Alderson; Carlos Caldas; Rebecca C Fitzgerald Journal: Gastroenterology Date: 2010-06-02 Impact factor: 22.682
Authors: Adam C Berger; Jeffrey Farma; Walter J Scott; Gary Freedman; Louis Weiner; Jonathan D Cheng; Hao Wang; Melvyn Goldberg Journal: J Clin Oncol Date: 2005-03-21 Impact factor: 44.544
Authors: Stephen G Maher; Charles M Gillham; Shane P Duggan; Paul C Smyth; Nicola Miller; Cian Muldoon; Kenneth J O'Byrne; Orla M Sheils; Donal Hollywood; John V Reynolds Journal: Ann Surg Date: 2009-11 Impact factor: 12.969