Page 261 - EJMO-9-3

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

significant upregulation of SNAI1, Slug, ZEB1, Twist, urea nitrogen, creatinine, systolic blood pressure, diastolic
and TNF-α in the liver metastasis group, as compared to blood pressure, and age. However, individuals with liver
both non-liver metastasis patients and adjacent normal metastases from CRC exhibited higher levels of circulating
tissue, underscores the central roles of these transcription fasting blood glucose, albumin, platelets, and blood urea
factors and inflammatory mediators in facilitating nitrogen. Notably, CEA, ALT, AST, and BMI showed
metastatic dissemination. This pattern of expression significant differences between the groups (p<0.05) as
aligns with the well-established understanding that EMT detailed in Table 2.
is a pivotal driver in cancer metastasis, endowing tumor It was observed that SNAI1, Slug, ZEB1, Twist, and
cells with enhanced migratory and invasive properties. TNF-α were most highly expressed in the liver metastasis
The concurrent downregulation of MTA3 in the liver group, whereas MTA3 was markedly decreased in this
metastasis group is particularly noteworthy, as it suggests group (Figure 1). The expression levels were significantly
a loss of EMT suppression, further promoting a pro- different when compared to both the non-liver metastasis
metastatic phenotype. The following presents a structured group and adjacent normal tissue. Further analysis using
framework based on mechanistic insights supported by univariate linear regression revealed that SNAI1, ZEB1,
research evidence:
Slug, Twist, and TNF-α markers were significantly
This framework (Table 1) highlights the central roles correlated with BMI (p≤0.05), while AST was correlated
of SNAI1, Slug, ZEB1, and Twist in EMT, supported by with SNAI1, Slug, Twist, and TNF-α only. Notably, MTA3
stromal interactions and pro-inflammatory mediators such showed no correlation with any of the four basic clinical
as TNF-α, whereas MTA3 acts as a suppressive regulator. characteristics (Table 3). Furthermore, each marker’s
Targeting these molecular nodes may disrupt metastatic association with cancer staging (T, N, and M) was
progression in colon cancer. specifically assessed. As presented in Table 4, all markers
Three patients in the non-liver metastasis group had a were found to significantly affect cancer stage. It is worth
history of diabetes mellitus (DM), four had hypertension, noting that MTA3 exhibited a negative Wald value, which
19 followed a high-protein diet, and two had cardiovascular indicates an inverse relationship with cancer staging.
disease (CVD), according to the patients’ medical records. The correlation between the expression of EMT markers
In the liver metastasis group, two individuals had a history (SNAI1, Slug, ZEB1, Twist, and TNF-α) and BMI highlights
of DM, one had hyperlipidemia, two had hypertension, six a potential link between metabolic status and the molecular
had a history of smoking, fifteen followed a high-protein mechanisms underlying metastasis (Table 3). Obesity and
diet, and two had CVD. None of the participants had a metabolic dysregulation have been increasingly recognized
history of hepatitis or alcohol consumption. There were as risk factors for cancer progression, and our findings
no significant differences (p≥0.05) between the two groups provide molecular evidence supporting this association.
in terms of hemoglobin, hematocrit, white blood cells, red Elevated BMI may create a microenvironment conducive
blood cells, platelets, fasting blood glucose, albumin, blood to EMT and metastasis, possibly through mechanisms such

Table 1. Framework summary of marker correlations
Marker Role in colon cancer Interaction partners Clinical relevance
SNAI1 Drives EMT, stemness, and stromal remodeling; upregulated by TWIST1, PDGF-BB, and Poor prognosis, metastasis 31,32
tumor ECM TGF-β1 30,31
Twist Enhances EMT and lymph node metastasis; synergizes with SNAI1, ALDH1 33 Reduced survival 33
SNAI1
Slug Supports EMT and stemness; context-dependent expression SNAI1 34 Clinical aggressiveness of tumors and
poor patient survival 34,35
ZEB1 Sustains mesenchymal state; potential downstream effector of SNAI1, TWIST1 36 Promotes the proliferation and invasion
SNAI1/TWIST1 of cancer 37
MTA3 Represses SNAI1; loss of MTA3 promotes SNAI1 31 Metastasis suppression 31
TNF-α Pro-inflammatory cytokine inducing EMT via NF-κB; modulates SNAI1, TWIST1 38,39 Linked to advanced disease 40
stromal-tumor crosstalk
Abbreviations: ALDH1: Aldehyde Dehydrogenase 1, ECM: Extracellular matrix; EMT: Epithelial-mesenchymal transition; MTA3: Metastasis-associated
protein 3; NF- κB: Nuclear factor kappa B; PDGF-BB; Platelet-derived growth factor subunit B; SNAI1: Snail family transcriptional repressor 1;
TGF-β1: Transforming growth factor-beta 1; TNF-α: Tumor necrosis factor-alpha; ZEB1: Zinc finger e-box binding homeobox 1.

Volume 9 Issue 3 (2025) 253 doi: 10.36922/EJMO025210202