Mateja Ilić*, Marija Cumbo Stikić, Aleksandra Vitkovac, Marija Lazić, Igor Davidović, Branko Tomić and Valentina Đorđević
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia
mateja.ilic [at] imgge.bg.ac.rs
Abstract
Colorectal cancer (CRC) is a heterogeneous disease, among the most common cancer types and third leading cause of cancer-related mortality in developed countries. Thrombin, along with its targets – protease-activated receptors (PARs) and fibrinogen, can facilitate the progression of CRC. However, the mechanisms behind this are not fully elucidated.
The aim of this study was to investigate the specific contribution of the thrombin-PAR-fibrinogen axis to CRC pathogenesis by analyzing corresponding gene expression patterns within the tumor microenvironment.
In this study, a publicly available spatial transcriptomics dataset was utilized, derived from a stage III-B colorectal cancer sample originating from the sigmoid colon and generated via the Visium HD platform. The raw reads were subsequently analyzed using Space Ranger v3.0 and the resulting gene-barcode matrix was processed using Scanpy v1.9.1. Following standard gene and barcode filtering and basic preprocessing, the dataset was annotated using Celltypist v1.7.1. The annotated dataset was then used to show the expression patterns of our genes of interest (F2, F2R, F2RL1, F2RL2, F2RL3, FGA, FGB, FGG).
Cell annotation recognized 17 types of cells in the analyzed sample. While prothrombin and fibrinogen genes (F2, FGA, FGB, FGG) expression pattern was uniform, PARs genes (F2R, F2RL1, F2RL2, F2RL3) expression was mapped predominately to regions recognized as CMS2 and CMS3 molecular subtype of CRC cells.
These findings indicate that the functional impact of thrombin, which is inherently dependent on the spatial distribution of PARs and fibrinogen, is distinctly manifested within specific CRC subtypes. However, the presented data are obtained from a single sample, and represent a “snapshot” of transcriptome in the moment of sampling. Consequently, future analyses involving a larger cohort encompassing diverse molecular subtypes of CRC are warranted to fully elucidate the broader clinical and biological significance of this axis in tumorigenesis.
Keywords: Colorectal cancer, thrombin, PAR
Acknowledgement: The public dataset used in this abstract is provided here: https://www.10xgenomics.com/platforms/visium/product-family/dataset-human-crc This project was partially funded by the Ministry of Science, Technological Development and Innovation of the Republic of Serbia (Contract No. 451-03-33/2026-03/200042).