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Serbian Association for Cancer Research SDIRSACR

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Novel MiRNA Signatures as Potential Biomarkers for Circulating Tumor Cell Status in Metastatic
Colorectal Cancer

Berkcan Dogan , Dilek Pirim , Ozgen Isik , Turkkan Evrensel 1,5
1,2
4
1,3
1 Bursa Uludag University, Institute of Health Sciences, Department of Translational Medicine, 16059, Bursa, Türkiye
2 Bursa Uludag University, Faculty of Medicine, Department of Medical Genetics, 16059, Bursa, Türkiye
3 Bursa Uludag University, Faculty of Arts & Science, Department of Molecular Biology and Genetics, 16059, Bursa, Türkiye
4 Bursa Uludag University, Faculty of Medicine, Department of General Surgery, 16059, Bursa, Türkiye
5 Bursa Uludag University, Faculty of Medicine, Department of Medical Oncology, 16059, Bursa, Türkiye

Keywords: biomarker; circulating tumor cells; metastatic colorectal cancer; microRNA; microarray.

Background: Colorectal cancer (CRC) is one of the most prevalent cancers and the second leading cause of cancer-
related deaths worldwide. Recent studies highlight the promising role of microRNAs (miRNAs) in predicting circulating
tumor cell (CTC) status. Combining miRNA and CTC analyses may offer a powerful approach to improving metastatic
cancer risk assessment. This study identified circulating miRNA signatures linked to CTC status in metastatic CRC.
Material and Methods: A total of 48 mCRC patients and 50 healthy individuals (HIs) were recruited. The CTC evaluation
was performed using AdnaTestColonCancer technology. Total RNA was isolated from whole blood, and miRNA expression
profiles were determined with the Agilent miRNA Microarray platform. Three miRNAs (hsa-miR-199a-5p, hsa-miR-326,
and hsa-miR-500b-5p) that were dysregulated (FC≥2 or ≤-2 and p<0.05) in CTC-positive and CTC-negative individuals
were analyzed through quantitative PCR using the miRCURY LNA miRNA PCR system. The diagnostic accuracy of these
miRNAs as potential biomarkers for distinguishing CTC-positive, CTC-negative, and HIs groups was evaluated by the
ROC analysis.
Results: The analyzed miRNAs exhibited statistically significant downregulation (p<0.05) in CTC-positive patients
compared to CTC-negative patients and HIs. ROC analyses revealed the area under the curve (AUC) values above
0.7, suggesting their effectiveness in distinguishing the CTC status of mCRC patients. Additionally, these miRNAs were
significant in the TCGA-COAD (Colon Adenocarcinoma) and TCGA-READ (Rectum Adenocarcinoma) RNA-Seq datasets
and associated with CRC in the Ingenuity Pathway Analysis.
Conclusion: Our findings highlight the potential utility of circulating miRNAs as a complementary method for identifying
the CTC status in mCRC. These results also provide new insights for new translational medicine applications in managing
mCRC through miRNA-based strategies for CRC-associated CTC detection.

Acknowledgments and funding: This study was supported by the Bursa Uludag University Scientific Research and
Project Unit (Grant numbers FOA-2021-625 and FHIZ-2023-1466) and the Scientific and Technological Research Council
of Turkey (TÜBİTAK) under Grant Number 224S591.

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Bridging Cancer Care and Research Gaps in Croatia: The CORN-CCI4EU Deep Dive

Sinisa Varga 1,2,3 , Petar Ozretic , Ivica Belina and Iva Kirac 1,3,5
1,4
1,3
1 Croatian Oncology Research Network
2 Dental Polyclinic Zagreb, Zagreb, Croatia
3 Institute for Gastroenterological Tumors, Zagreb, Croatia
4 Institute Rudjer Boskovic
5 Coalition of Patient Associations
6 Sestre milosrdnice University Hospital Center, Zagreb Croatia

Cancer remains a leading cause of death in Europe, and Croatia faces persistent regional disparities in access to
comprehensive oncology services. The EU-funded CORN-CCI4EU Deep Dive, launched under the CCI4EU horizon
project, aims to address these inequities by supporting the development of Comprehensive Cancer Infrastructures
(CCIs) in Croatia. The project’s goal is that by 2030, at least 90% of patients who could benefit from multidisciplinary

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