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Serbian Association for Cancer Research SDIRSACR

P35

Diagnostic potential of SMAD7 and SMAD4 expression and their ratio in locally advanced rectal cancer
and colorectal liver metastasis

Jovana Rosic Stojkovic , Sandra Dragicevic , Marko Miladinov , Aleksandar Bogdanovic , Goran Barisic , Aleksandra
1
3
2
1,3
3
Nikolic , Katarina Zeljic 4
2
1Faculty of Medicine, University of Belgrade, Belgrade, Serbia
2Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
3Clinic for Digestive Surgery – First Surgical Clinic, University Clinical Center of Serbia, Belgrade, Serbia
4Faculty of Biology, University of Belgrade, Belgrade, Serbia
Keywords: Colorectal Cancer, Metastasis, Rectal Cancer, SMAD7, SMAD4

Background: Given the important role of SMAD signaling in mediating the TGF-β pathway activity in cancer, and the
critical functions of both the inhibitory SMAD7 and the common mediator SMAD4 in this process, this study investigated
the diagnostic relevance of the mRNA expression levels of these two genes and their ratio in locally advanced rectal
cancer (LARC) and colorectal liver metastases (CLM).
Patients and Methods: Relative expression levels of SMAD7 and SMAD4 were measured in tumor and corresponding
non-tumor tissues from 19 LARC and 16 CLM patients using quantitative real-time PCR (qPCR) and normalized to
the housekeeping gene GAPDH. To evaluate the potential of the investigated gene expression levels and their ratio
in distinguishing tumor from matched non-tumor tissues in LARC and CLM, Receiver Operating Characteristic (ROC)
analysis was performed, and their translational value as diagnostic biomarkers was assessed based on the area under
the curve (AUC), 95% confidence intervals (CI), and p-values. AUC values below 0.6 were considered poor, between 0.6
and 0.7 fair, 0.7 to 0.8 good, 0.8 to 0.9 very good, and above 0.9 excellent for the discriminatory power of the biomarker.
Optimal cut-off values for differentiating tumor from non-tumor tissue were determined for each expression pattern
using the maximum value of Youden's index (Youden's index = sensitivity + specificity – 1). Expression patterns were
considered useful biomarkers if AUC>0.600 and p<0.05.
Results: In LARC patients, SMAD4 gene expression and the SMAD7/SMAD4 ratio demonstrated good diagnostic
potential for distinguishing tumor from matched non-tumor tissue (AUC=0.731, p=0.015 and AUC=0.745, p=0.010,
respectively), whereas SMAD7 expression alone did not perform well as a diagnostic biomarker (AUC=0.593, p=0.328).
In CLM patients, SMAD7 and SMAD4 expression showed good to excellent diagnostic performance in distinguishing
metastatic from matched non-tumor liver tissue (AUC=0.719, p=0.035 and AUC=0.973, p<0.0001, respectively), while
the SMAD7/SMAD4 ratio did not prove to be a reliable diagnostic biomarker (AUC=0.629, p=0.214).
Conclusions: SMAD4 expression and the SMAD7/SMAD4 ratio showed promising diagnostic potential in LARC, while
both SMAD7 and SMAD4 expression demonstrated strong discriminatory power in CLM, underscoring the need for
validation in larger, independent patient cohorts.

Acknowledgments and funding: This work was supported by the strategic project of the Serbian Academy of Sciences
and Arts “Molecular basis of response to chemoradiotherapy in rectal cancer – MOHERATEKA” (F-69), and the Ministry
of Science, Technological Development and Innovation of the Republic of Serbia (Grant No. 451-03-137/2025-03/
200110).

P36

ALDOA-212 noncoding transcript – a potential biomarker for colorectal cancer

Jelena Karanović1, Anastasija Tomović1, Jovana Despotović1, Stefan Kmezić2, Aleksandra Nikolić1

1Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
2Clinic for Digestive Surgery, University Clinical Centre of Serbia, Belgrade, Serbia

Keywords: biomarker, colorectal cancer, noncoding RNA

Background: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related

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