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Updated: May 27, 2026
Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
Suppressor of cytokine signaling 4 detected as a novel gastric cancer suppressor gene using double combination array
Daisuke Kobayashi1, Shuji Nomoto, Yasuhiro Kodera
1Department of Surgery II, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Background:
Molecular mechanisms behind the oncogenesis of gastric cancer (GC) have yet to be identified.
Methods:
A novel candidate tumor-suppressor gene, which is also associated with inhibition of epidermal growth factor (EGF), was sought by means of double combination array analysis for use as a prognostic marker of GC. This consisted of expression array and single nucleotide polymorphism array analysis, along with a literature search. Cancerous and noncancerous tissues from an 82-year-old man with GC were analyzed simultaneously.
Results:
The expression array and literature search identified that the suppressor of cytokine signaling 4 (SOCS4), a negative feedback regulator of EGF signaling, had significantly attenuated expression in tumor tissue. Although chromosomal deletion was not found at 14q22 where SOCS4 is located, numerous CpG sites were observed in the promoter region of the SOCS4 gene. Several GC cell lines showed reactivation of SOCS4 mRNA expression after treatment with 5-aza-2'-deoxycytidine. Using surgically resected specimens, we found that 40 of 50 (80%) tumor tissues exhibited promoter hypermethylation of the SOCS4 gene. Consequently, SOCS4 expression in tumor tissues was significantly weaker than in noncancerous counterparts (P < 0.0001). In the survival analysis, SOCS4 hypermethylation was associated with a poor prognosis of GC patients (P = 0.0320).
Conclusions:
Double combination array analysis suggested that SOCS4 could be a novel candidate for further exploration as a tumor-suppressor gene in GC. Hypermethylation was the mechanism by which SOCS4 was silenced and was implicated in the development of GC. SOCS4 methylation might be an informative marker in predicting the prognosis.
Insights
Gastric cancer (GC) development involves silencing of the SOCS4 gene through promoter hypermethylation. This methylation is linked to poor prognosis and may serve as a novel prognostic marker for GC patients.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- The molecular mechanisms driving gastric cancer (GC) oncogenesis remain largely unidentified.
- Understanding these mechanisms is crucial for developing effective diagnostic and therapeutic strategies.
Purpose of the Study:
- To identify novel tumor-suppressor genes involved in GC development.
- To investigate the role of the suppressor of cytokine signaling 4 (SOCS4) gene in GC.
- To evaluate SOCS4 as a potential prognostic marker for GC.
Main Methods:
- Utilized double combination array analysis (expression and SNP arrays) and literature review.
- Analyzed cancerous and noncancerous tissues from GC patients.
- Investigated SOCS4 gene expression and promoter methylation status.
- Assessed the correlation between SOCS4 hypermethylation and patient prognosis.
Main Results:
- Identified significantly attenuated SOCS4 expression in GC tumor tissues compared to noncancerous tissues.
- Found widespread promoter hypermethylation of the SOCS4 gene in 80% of GC tumor samples.
- Demonstrated that SOCS4 hypermethylation was significantly associated with a poorer prognosis in GC patients.
- Observed reactivation of SOCS4 expression after demethylating agent treatment in GC cell lines.
Conclusions:
- SOCS4 is a potential tumor-suppressor gene in gastric cancer.
- Promoter hypermethylation is a key mechanism for SOCS4 gene silencing in GC.
- SOCS4 methylation status may serve as a valuable prognostic biomarker for predicting GC patient outcomes.
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