Evaluation of AKR1B1 expression in the stromal compartment of colorectal tumors

Research project within the scientific and technological cooperation between the Ministry of Education, Science and Technological Development of the Republic of Serbia and the Council for Scientific and Technological Research of Turkey, 2021-2024
Principal Investigator: Dr Aleksandra Nikolic
Participants from IMGGE: Dr Sandra Dragicevic, Jovana Despotovic, Tamara Babic

Aldo keto reductases (AKRs) are a large family of oxidoreductases that can utilize electrons from NADPH and reduce substrates including glucose, retinals and a number of drugs. AKRs are strongly implicated in diabetic pathophysiology. We have recently shown that the expression of AKR1B1 and AKR1B10, two of the most well studied isoforms of AKRs, play crucial roles in the progression of colorectal cancer (CRC). These genes can be considered as biomarkers since a combined signature of high expression of AKR1B1 and low expression of AKR1B10 was significantly correlated with poor disease free survival in CRC, a high epithelial to mesenchymal transition (EMT) score and was associated with a Consensus Molecular Subtype (CMS)-4 phenotype characterized by strong mesenchymal features. It is being increasingly appreciated that the tumor microenvironment contributes significantly to the initiation and progression of many different cancer types. We carried out a preliminary bioinformatics assessment and observed that, surprisingly, the expression of AKR1B1 (but not AKR1B10) was significantly higher in the stromal compartment compared to the epithelial compartment of CRC tissues. These data suggest that the stromal expression of AKR1B1 may contribute towards the prognostic predictions observed for this gene. With this proposal we aim to establish for the first time which component of the stromal compartment contributes towards the expression of AKR1B1 in CRC and whether the stromal expression of AKR1B1 contributes towards the prognostic value of the gene. Moreover, we will examine whether AKR1B1 expression can predict response to neoadjuvant treatment in CRC, which has not been studied before to the best of our knowledge. Therefore, the findings of this study have a high potential of providing valuable information regarding the stromal effect on the expression of prognostic/predictive biomarkers to the field of cancer biology.