Page 263 - EJMO-9-3

Eurasian Journal of
Medicine and Oncology Metastasis gene expression in colorectal cancer

A Table 4. Ordinal regression analysis
Response Predictor Wald value p‑value
Stage (TNM) SNAI1 3.006 0.022*
Stage (TNM) ZEB1 1.725 0.031*
Stage (TNM) Slug 2.018 0.016*
Stage (TNM) Twist 1.922 0.028*
B Stage (TNM) MTA3 −3.443 0.035*
Stage (TNM) TNF-α 5.813 0.006*
Note: * Significant with p≤0.05.
Abbreviations: M: Metastasis; MTA3: Metastasis-associated protein 3;
N: Node; SNAI1: Snail family transcriptional repressor 1; T: Tumor;
TNF-α: Tumor necrosis factor-alpha; ZEB1: Zinc finger e-box binding
homeobox 1.
C
expression profiles, these clinical markers may serve as a
potential composite biomarker panel for risk stratification
and early detection of metastatic spread.

The clinical significance of these molecular findings
is reinforced by the ordinal regression analysis, which
demonstrated that all examined markers significantly
D influence cancer stage (T, N, M). The negative Wald value
for MTA3 is particularly intriguing, indicating that higher
MTA3 expression is associated with a lower cancer stage
and, conversely, that its downregulation is linked to more
advanced disease. This inverse relationship supports
the hypothesis that MTA3 acts as a tumor suppressor by
antagonizing EMT and maintaining epithelial integrity.

E Therapeutically, restoring MTA3 function or mimicking
its activity could represent a novel strategy to impede
metastatic progression in colon cancer.

4. Discussion
Beyond the molecular insights, the clinical translation of
these findings holds significant promise for improving
patient outcomes in CRC. The identification of SNAI1 as a
F
central regulator of EMT and chemoresistance suggests that
SNAI1-targeted therapies could be developed to overcome
treatment resistance, a major challenge in advanced CRC.
Small molecule inhibitors or RNA interference strategies
aimed at reducing SNAI1 expression, or disrupting its
stabilization pathways such as the AKT/GSK-3β axis,
7
may sensitize tumors to conventional chemotherapeutics.
Figure 1. (A-F) Relative gene expression of markers in CRC patients with Furthermore, the interplay between SNAI1 and
non-liver and liver metastasis, measured by RT-qPCR and compared with inflammatory cytokines such as TNF-α highlights the
adjacent normal tissue
Note: *Significant difference between groups by independent sample potential for combinatorial therapies that simultaneously
t-test (p≤0.05). target both EMT and inflammation. For instance, anti-
Abbreviations: CRC: Colorectal cancer; LM: Liver metastasis; TNF-α agents, already in clinical use for inflammatory
MTA3: Metastasis-associated protein 3; N: Adjacent normal tissue; bowel disease, could be repurposed or combined with EMT
Non-LM: Non-liver metastasis; SNAI1: Snail family transcriptional repressor 1;
TNF-α: Tumor necrosis factor-alpha; ZEB1: Zinc finger e-box binding inhibitors to suppress tumor progression and metastasis in
homeobox 1. CRC patients with elevated TNF-α signaling.

Volume 9 Issue 3 (2025) 255 doi: 10.36922/EJMO025210202