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Eurasian Journal of
Medicine and Oncology Metastasis gene expression in colorectal cancer
with the results obtained in this study, where AST levels Funding
were higher in the metastasis group than in the non-
metastasis group (Table 2). None.
Therapeutic implications for targeting SNAI1, ZEB1, Conflict of interest
Slug, Twist, MTA3, and TNF-α or their regulators The authors declared that there were no conflict of interest
show promise. Natural compounds sensitize cells to in this work.
chemotherapy by disrupting EMT and inhibiting cancer
development, while stromal inhibition of SNAI1, ZEB1, Author contributions
Slug, Twist, MTA3, and TNF-α could mitigate pro-
tumorigenic signaling. However, partial EMT states Conceptualization: Adeodatus Yuda Handaya, Hendra
may persist as reservoirs for recurrence, necessitating Susanto
combination therapies. As shown in Table 4, the markers Formal analysis: All authors
used in this study affect cancer development, as expressed Investigation: All authors
in the T, N, and M (stage) grading scores. Methodology: Hendra Susanto, Adeodatus Yuda Handaya
Writing–original draft: Adeodatus Yuda Handaya, Moch
In conclusion, SNAI1 emerges as the dominant Sholeh
EMT-TF in colon cancer, modulated by TNF-α and stromal Writing–review & editing: Adeodatus Yuda Handaya, Moch
interactions. ZEB1, Slug, and Twist play ancillary roles, Sholeh
while MTA3’s involvement remains speculative. Therapeutic
strategies must account for SNAI1’s multifaceted regulation Ethics approval and consent to participate
and the complexity of the tumor microenvironment. The participants consented to complete the informed
However, we recognize several limitations in this study, consent form for the clinical observational study. With
including: (a) the lack of a comprehensive database for the certificate of ethics number: KE/FK/0938/EC/2021,
patient baseline data, and (b) the focus on profiling the this clinical study was authorized by the IRB, Faculty
expression of several markers in CRC patient tumors of Medicine, Universitas Gadjah Mada, Indonesia, in
without supporting or validating data from additional tests, accordance with the Declaration of Helsinki.
such as somatic mutation analysis. Future studies should
involve larger sample sizes, comparisons across racial Consent for publication
groups of clinical patients, and further laboratory analysis. Not applicable, because the respondents’ identities have
A comprehensive correlational approach that includes been completely masked, and they have also agreed in the
microscopic, serological, and bioinformatics analysis will “written consent to participate” section that the samples
be essential to support these initial findings. will be used for further research purposes.
5. Conclusion Availability of data
Through this study, it was found that SNAI1, ZEB1, Slug, All the datasets generated in the current study are available
Twist, and TNF-α were associated with cancer progression from the corresponding author based on reasonable
toward metastasis, as their expression levels increased request.
accordingly. In contrast, MTA3, a known metastasis
suppressor, showed relatively lower expressing during References
metastasis progression. In addition, SNAI1, ZEB1, Slug,
Twist, and TNF-α were also correlated with BMI and AST 1. Klimeck L, Heisser T, Hoffmeister M, Brenner H. Colorectal
cancer: A health and economic problem. Best Pract Res Clin
levels
Gastroenterol. 2023;66:101839.
Acknowledgments doi: 10.1016/j.bpg.2023.101839
The authors would like to express our deepest gratitude to 2. Sharzehan MAK, Sito H, Abdullah N, et al. Association
the PhD Biotechnology team at Malang State University for between CYP2E1 polymorphisms and colorectal
conducting this research, as well as to our partners from cancer risk: A systematic review and meta-analysis. Sci
the Division of Digestive Surgery, Department of Surgery, Rep. 2022;12(1):20149.
Faculty of Medicine, Public Health and Nursing, Gadjah doi: 10.1038/s41598-022-24398-w
Mada University, and Dr. Sardjito General Hospital, 3. Islam MR, Aziz MA, Shahriar M, Islam MS. Polymorphisms
Yogyakarta, Indonesia, for their assistance with clinical in IL-17A gene and susceptibility of colorectal cancer in
support and respondent preparation. bangladeshi population: A case-control analysis. Cancer
Volume 9 Issue 3 (2025) 257 doi: 10.36922/EJMO025210202

