Supportive Care in Cancer

, Volume 23, Issue 11, pp 3165–3172 | Cite as

Pre-therapy mRNA expression of TNF is associated with regimen-related gastrointestinal toxicity in patients with esophageal cancer: a pilot study

  • J. M. Bowen
  • I. White
  • L. Smith
  • A. Tsykin
  • K. Kristaly
  • S. K. Thompson
  • C. S. Karapetis
  • H. Tan
  • P. A. Game
  • T. Irvine
  • D. J. Hussey
  • D. I. Watson
  • D. M. K. Keefe
Original Article



Esophageal cancer has a high mortality rate, and its multimodality treatment is often associated with significant rates of severe toxicity. Effort is needed to uncover ways to maximize effectiveness of therapy through identification of predictive markers of response and toxicity. As such, the aim of this study was to identify genes predictive of chemoradiotherapy-induced gastrointestinal toxicity using an immune pathway-targeted approach.


Adults with esophageal cancer treated with chemotherapy consisting of 5-fluorouracil and cisplatin and 45–50 Gy radiation were recruited to the study. Pre-therapy-collected whole blood was analyzed for relative expression of immune genes using real-time polymerase chain reaction (RT-PCR). Gene expression was compared between patients who experienced severe regimen-related gastrointestinal toxicity vs. those experiencing mild to moderate toxicity.


Blood from 31 patients were analyzed by RT-PCR. Out of 84 immune genes investigated, TNF was significantly elevated (2.05-fold, p = 0.025) in the toxic group (n = 12) compared to the non-toxic group (n = 19). Nausea and vomiting was the most commonly documented severe toxicity. No associations between toxicity and response, age, sex, histology, or treatment were evident.


This study supports evidence of TNF as a predictive biomarker in regimen-related gastrointestinal toxicity. Confirming these findings in a larger cohort is warranted.


Toxicity Chemoradiation Esophageal cancer Mucositis RT-PCR 



We acknowledge the assistance provided by Bronwen Jones and Jeff Bull in patient identification, Associate Professor Peter Devitt and DrNimitSinghal for patient recruitment, Mr Tim Bright for tumor response classification, and Mark Van der Hoek for RNA bioanalysis.

Conflict of interest

The authors have no conflict of interest associated with publication of this manuscript.

Supplementary material

520_2015_2696_MOESM1_ESM.docx (22 kb)
Supplementary Table 1(DOCX 22 kb)
520_2015_2696_MOESM2_ESM.docx (19 kb)
Supplementary Table 2(DOCX 19 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • J. M. Bowen
    • 1
  • I. White
    • 2
  • L. Smith
    • 3
  • A. Tsykin
    • 4
  • K. Kristaly
    • 2
  • S. K. Thompson
    • 3
  • C. S. Karapetis
    • 5
  • H. Tan
    • 6
  • P. A. Game
    • 3
  • T. Irvine
    • 7
  • D. J. Hussey
    • 7
  • D. I. Watson
    • 7
  • D. M. K. Keefe
    • 2
  1. 1.School of Medical SciencesUniversity of AdelaideAdelaideAustralia
  2. 2.School of MedicineUniversity of AdelaideAdelaideAustralia
  3. 3.Discipline of SurgeryUniversity of AdelaideAdelaideAustralia
  4. 4.Centre for Cancer BiologySA PathologyAdelaideAustralia
  5. 5.School of MedicineFlinders UniversityBedford ParkAustralia
  6. 6.RAH Cancer CentreRoyal Adelaide HospitalAdelaideAustralia
  7. 7.Department of SurgeryFlinders UniversityAdelaideAustralia

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