Page 151 - SRPSKO DRUŠTVO ISTRAŽIVAČA RAKA

SDIRSACR Oncology Insights

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The critical role of ADAMTS8 expression deregulation in forwarding vascular invasion in rectal carcinoma

Bojana Kožik , Tarik Čorbo , Naris Pojskić , Lejla Kapur Pojskić , Lidija Todorović , Ana Božović , Ana Kolaković 1
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1Laboratory for Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences, National Institute of Republic of Serbia,
University of Belgrade, Belgrade, Serbia
2Institute for Genetic Engineering and Biotechnology, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
Keywords: rectal carcinoma, vascular invasion, ADAMTS8

Background: Rectal carcinoma (RC) accounts for approximately 30% of all colorectal carcinomas (CRC) and is recognized
as a distinct clinical entity with unique causes and treatment strategies. Aside from lymphatic invasion, RC can spread in
several vascular ways previously identified and validated as prognostic markers. Vascular invasion (VI) has consistently
been shown to be associated with poor prognosis, both when detected by pathology and radiology methods, however,
the molecular basis of VI is poorly studied. Several mechanisms may contribute to the VI process, including epithelial-
mesenchymal transition (EMT), remodeling of the extracellular matrix (ECM), and angiogenesis. This integrative
study was conducted with the aim of identifying genes and pathways specific for a VI-positive rectal adenocarcinoma
phenotype.
Material and Methods: Using cBioPortal dataset platform, we examined mRNA expression and methylation data of 41
pre-selected, literature-based genes proven to be involved in regulating EMT, ECM, and angiogenesis during colorectal
carcinogenesis and their potential association with vascular invasion as a clinical feature in a RC dataset consisting of
78 samples, which were filtered from the COADREAD TCGA (Firehose Legacy) dataset.
Results: Among 41 tested gene candidates, only ADAMTS8 showed a significant association between lower ADAMTS8
mRNA expression and vascular invasion was detected (p=0.039, tested by Mann-Whitney U test). In addition, methylome
analysis strongly suggests promoter methylation of the ADAMTS8 gene, as a mechanism of epigenetic gene silencing,
since in this cohort ADAMTS8 mRNA expression significantly correlates with ADAMTS8 methylation level (p=0.012, r=-
0.263, Spearman’s test of correlation). Moreover, we observed a tendency toward association between higher level of
ADAMTS8 methylation and vascular invasion (p=0.087, tested by Mann-Whitney U test). Interestingly, protein-protein
interaction analysis among protein products of tested 41 genes on STRING platform revealed that only ADAMTS8
protein formed a distinct cluster, displaying no interactions with any other queried proteins. Observed associations
require further functional and experimental analysis to elucidate the exact role of ADAMTS8 expression deregulation
in forwarding vascular invasion RC.
Conclusions: Obtained results have potential clinical utility, providing new approaches for developing targeted therapies
for VI-positive rectal cancer, and require in vitro validation.

Acknowledgments and funding This work is the result of collaboration within COST Translacore CA21154.

P60

Deep learning on combined multistain and color-depth histology enhances early breast cancer prognosis

Yifei Lin1, Xingyu Li1, Jelena Milovanovic2, Nataša Todorovic Rakovic2, Velicko Vranes3, Tijana Vujasinović2, Ksenija
Kanjer2, Marko Radulovic2

1Electrical & Computer Engineering Department, Faculty of Engineering, University of Alberta, Edmonton, Canada
2Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia
3Department of Basic and Environmental Science, Instituto Tecnológico de Santo Domingo (INTEC), Santo Domingo, Dominican
Republic

Keywords: breast cancer, deep learning, distant metastasis, histopathology, microscopy, multicolor-depth, multistain,
pan-cytokeratin, prognosis, ResNet

Background: Traditional clinicopathological markers of breast cancer outcome are now supplemented by molecular
assays such as gene-expression panels, microRNA signatures, circulating tumour cells, proliferation markers, cytokines,

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