P12: Resistance to Chemo Radiation in Rectal Cancer Can Potentially be Predicted by Proteomic Analyses

ePoster Presenter(s)

Tobias Zott

Resident
Medical University Vienna, Department of Surgery
Vienna, Wien, Austria

Submitter(s)

Tobias Zott

Resident
Medical University Vienna, Department of Surgery
Vienna, Wien, Austria

Author(s)

Tobias Zott

Resident
Medical University Vienna, Department of Surgery
Vienna, Wien, Austria
BA

Bileck Andrea, n/a

Researcher
University Vienna, Department of Analytical Chemistry, United States
GP

Günter Plessl-Walder, n/a

Researcher
University Vienna, Department of Analytical Chemistry, United States
CG

Christopher Gerner, n/a

Head of department
University Vienna, Department of Analytical Chemistry, United States
GS

Gerd Silberhumer, n/a

Senior physician
Medical University Vienna, Department of Surgery, United States

Introduction: Chemoradiation prior to surgery in locally advanced rectal cancer results in reduced local recurrence rates and increased rates of sphincter preservation. Unfortunately, this neoadjuvant therapy is not effective in all colorectal cancer patients. Prognostic marker molecules regarding the sensitivity to radiation in each individual would be of great interest, because patients not responding to radiation could be protected from side effects of radiation and selected for other treatment options.

Methods:

Aim of this study was to assess the suitability of formalin fixed paraffin embedded (FFPE) samples for LC-MS based proteomics analysis by evaluating known tumor markers and searching for marker molecules potentially distinguishing responders from non-responders. Therefore, a comprehensive LC-MS based proteomics study was performed on FFPE colorectal (n=50) and control (n=39) tissue samples of patients having received neoadjuvant chemoradiation before surgery.

Results:

Out of 50 patients, response to radiation was observed in 27 patients, whereas 23 patients did not show any response to radiation. As a result, a total number of 1680 robustly expressed proteins were identified in FFPE tissues samples. Comparing colorectal tumor and control samples revealed 66 proteins with significantly different abundance values. Thereof, 49 proteins were significantly higher in tumor samples compared to 17 proteins enriched in control samples. Regarding the comparison of responders and non-responders, a total number of 281 significantly regulated proteins were identified. Thereof, 277 proteins were up-regulated in non-responders whereby the carcinoembryogenic antigen-related cell adhesion molecules (CEACAM) 1, 5 and 6 showed the best significance scores. Gene Ontology term enrichment analysis revealed cytoplasmic translation as the main enriched biological processes with a p-value of 1,2E-19. Furthermore, proteins belonging to the minichromosome maintenance protein complex (MCM), i.e. MCM2, MCM3, MCM4, MCM6 and MCM7 were found to be significantly higher in non-responders compared to responders. MCM3 has been already describe to promote radio-resistance in hepatocellular carcinoma by activating the NF-κB pathway.

Conclusions: This study clearly demonstrates the suitability of FFPE samples for proteomic analysis in order to investigate molecular mechanisms mediating resistance to radiotherapy. Significant differences were analysed between tumor and control samples as well es responders and non-responders to neoadjuvant treatment.

Learning Objectives:

... better understand the mechanism of radio resistance.
... deepen their understanding of proteomic research.
... list proteins characteristic for tumor tissue.