TaqMan^® Low-Density Arrays and Analysis by Artificial Neuronal Networks Predict Response to Neoadjuvant Chemoradiation in Esophageal Cancer

Abstract

Aims: Neoadjuvant radiochemotherapy of locally advanced esophageal cancer is only effective for patients with major histopathological response. A total of 17 genes were selected to predict histopathologic tumor response to chemoradiation (cisplatin, 5-fluorouracil, 36 Gy). Materials & methods: For gene-expression analysis quantitative TaqMan^® low-density arrays were applied. Expression levels in pretreatment biopsies of 41 patients (cT2–4, Nx, M0) were compared with the degree of histopathologic regression in resected specimens applying univariate, multivariate and artificial neuronal network analyses. Results: Dihydropyrimidine dehydrogenase was identified as an independent predictor associated with major response (p < 0.002). Multivariate analysis of the marker combination provided response prediction with 75.0% sensitivity, 81.0% specificity and 78.1% accuracy. Artificial neuronal network analysis was the best predictive model for major histopathologic response (80% sensitivity, 90.5% specificity and 85.4% accuracy), representing a clinically practical system. Conclusion: Low-density-array RT-PCR analyzed by artificial neuronal network predicts histopathologic response to neoadjuvant chemoradiation in our patient collective, and could be used to further individualize treatment strategies in esophageal cancer.

KEYWORDS::

• chemosensitivity
• DPYD
• gene expression
• multimodality treatment
• neuronal networks
• prognosis
• radiosensitivity
• RT-PCR

Acknowledgements

We thank Michaela Heitmann, Susanne Neiss, Stephanie Schreckenberg and Anke Wienand-Dorweiler for their excellent technical support.

Financial & competing interests disclosure

This study was supported by the Marga and Walter Boll-Stiftung, Cologne, Germany. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was supported by the Marga and Walter Boll-Stiftung, Cologne, Germany. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.