Page 77 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

P37

In silico analysis of predictive biomarkers for neoadjuvant chemoradiotherapy in locally
advanced rectal cancer

2
3
1
1
Aleksandra Stefanović , Mladen Marinković , Marija Ostojić , Vladimir Nikolić , Suzana Stojanović-
2,4
1
1
Rundić , Radmila Janković , Milena Čavić
1 Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia
2 Clinic for Radiation Oncology and Diagnostics, Department of Radiation Oncology, Institute for Oncology and
Radiology of Serbia, Belgrade, Serbia
3 Clinic for Medical Oncology, Department for Gastrointestinal and Lung Cancers, Institute for Oncology and
Radiology of Serbia, Belgrade, Serbia
4 Faculty of Medicine, University of Belgrade, Belgrade, Serbia

Background: Standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant
chemoradiotherapy (nCRT). Response to therapy varies among patients and there is a huge need for
discovering biomarkers that would enable better prediction of the response. The aim of this study was to
evaluate predictive markers for CRT in search for LARC patients that might benefit from no immediate
radical surgery, but rather an enrollment in a watch and wait approach. Material and methods: We
searched the publicly available NCBI database Gene Expression Omnibus (GEO). Gene Set Enrichment
Analysis (GSEA) was performed on selected data sets using keywords rectal cancer, CRT and response. LARC
patients were divided into groups according to the pathohistological Mandard tumor regression grading
(TRG) system as Responders (TRG 1-2) and Non-responders (TRG 3-5). Hallmark, KEGG, and Reactome gene
sets were used to compare expression levels between the two groups. Results: Gene expression sets of
inflammatory response-related signaling pathways were found to significantly correlate with good
response to CRT (p<0.05; FDR<0.25) in patients with LARC. Overlapping the results the following genes
were discovered as predictors of favorable response: CXCL10, IDO1, CXCL9, CYBB, TGFB2, PLAU, PDGFRB,
INHBA, IL24, HGF, and IL6. Conclusion: A set of inflammatory response-related genes were found to
correlate with favorable response to CRT. Validation of these in silico discovered biomarkers is under way
in a cohort of 94 LARC patients and might lead to a better selection of patients who could benefit from a
wait and watch approach thus increasing their quality of life.
Keywords: GSEA, nCRT, rectal cancer, inflammatory response.

Acknowledgements: This study is supported by the Ministry of Education and Science of the Republic of
Serbia (Agreement No. 451-03-9/2021-14/200043). This article is based upon work from COST Action
CA17118, supported by COST (European Cooperation in Science and Technology); www.cost.eu. MC is
supported by the Science Fund of the Republic of Serbia (PROMIS TRACEPIGEN project No. 6060876).

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