Page 114 - SRPSKO DRUŠTVO ISTRAŽIVAČA RAKA

Serbian Association for Cancer Research SDIRSACR

SESSION 3

TUMOR MICROENVIRONMENT - FRIEND OF FOE

P17
Exploring the expression and prognostic utility of NISCH in primary and metastatic rectal cancer

Jovana Despotović , Vladica Ćuk , Jovan Juloski , Aleksandar Bogdanović , Danijel Galun , Jelena Grahovac 5
3,4
1
2,3
2,3
3,4
1Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
2Zvezdara University Clinical Centar, Nikola Spasić Surgical Clinic, Belgrade, Serbia
3School of Medicine, University of Belgrade, Belgrade, Serbia
4Clinic for Digestive Surgery, First Surgical Clinic, University Clinical Center of Serbia, Belgrade, Serbia
⁵Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia
Keywords: liver metastasis, NISCH, prognostic biomarker, rectal cancer

Background: Rectal adenocarcinoma (READ) ranks 8th in terms of incidence and 10th in mortality rates, representing
a significant public health concern worldwide. As a result, new diagnostic and prognostic biomarkers are urgently
needed. NISCH has been identified as both a tumor suppressor and a positive prognostic marker in breast and ovarian
cancers. Recent analyses of NISCH across various tumor types have revealed its context-dependent role. However,
NISCH has not been extensively studied in READ. The aim of this study was to analyze NISCH expression in both primary
and metastatic READ and evaluate its prognostic potential.
Material (Patients) and Methods: NISCH levels in normal and READ samples were obtained through Xena Functional
Genomics Explorer, TIMER, and GEPIA2 online tools. Additionally NISCH was analysed by RT-qPCR in our two cohorts
with paired samples: cohort 1 consisted of 28 patients with primary READ with adjacent normal rectal tissue, and the
cohort 2 with 17 patients with rectal cancer with liver metastasis (RCLM) and adjacent normal liver tissue. GAPDH
levels were used for normalization. Data were analysed using the 2-dCt method. Kaplan–Meier (KM) analysis was used
to evaluate overall survival (OS) and disease-free survival (DFS) in cohort 1 and time to recurrence (TTR) in cohort 2
based on NISCH expression.
Results: In silico analyses using Xena and TIMER online tools revealed no significant difference in NISCH expression
between READ and normal rectal tissue. In contrast, GEPIA2 analysis indicated that NISCH was reduced in READ. Due
to these inconsistent findings across databases, we further evaluated NISCH expression on our cohorts. No significant
difference in NISCH expression was observed between READ and adjacent normal rectal tissue in cohort 1. Also, there
was no difference in NISCH expression between primary and metastatic READ from cohort 2. However, NISCH was
significantly downregulated in RCLM compared to healthy liver tissue. KM analysis showed no association between
NISCH expression and OS or DFS (cohort 1) or TTR (cohort 2).
Conclusions: While NISCH expression did not differ between primary READ, adjacent normal tissue, or metastatic
lesions, it was significantly downregulated in liver metastases compared to healthy liver tissue, suggesting a potential
role in the metastatic liver microenvironment. NISCH expression showed no prognostic value for OS, DFS or recurrence
in the analyzed rectal cancer cohorts.

Acknowledgments and funding: This research was supported by the Science Fund of the Republic of Serbia, PROMIS
Grant No. 6056979, REPANCAN, by the Ministry of Education, Science and Technological Development of the Republic
of Serbia Agreement No. 451-03-66/2024-03/200043 and 451-03-136/2025-03/200042, and the European Union’s
Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 891135.

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