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Updated: Aug 9, 2026
Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
Identification of secernin 1 as a novel immunotherapy target for gastric cancer using the expression profiles of cDNA
Takako Suda1, Takuya Tsunoda, Naotaka Uchida
1Department of Surgery and Bioengineering, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Abstract:
Despite the discovery of multiple TAAs, only a limited number is available for clinical application, particularly against epithelial malignancies. In this study we searched for novel TAAs using expression profiles of gastric cancer examined with cDNA microarray, and identified the SCRN1 gene as a candidate. SCRN1 was confirmed to be expressed in five out of seven gastric cancers with semiquantitative RT-PCR. With Northern blot analysis, it was detected abundantly in the testis and ovary, but it was barely detectable in 14 other normal human adult organs. Colony formation assay revealed that its augmented expression is associated with promoted cell growth. As these expression profiles and functional features of SCRN1 appeared to be compatible with the characteristics of the hypothesized ideal TAAs, we examined whether SCRN1 protein contains antigenic epitope peptides restricted to HLA-A*0201. We synthesized the candidate peptides derived from SCRN1, and tried to induce CTLs with each peptide. The CTL clones were successfully induced with a peptide SCRN1-196 (KMDAEHPEL), and they lyzed not only the peptide-pulsed targets but also the tumor cells expressing both SCRN1 and HLA-A*0201 endogenously. These results strongly suggest that SCRN1-196 is an epitope peptide restricted to HLA-A*0201. Furthermore, we synthesized an anchor-modified peptide SCRN1-9 V (KMDAEHPEV), in which leucine at position 9 was substituted for valine to increase the binding affinity to the HLA-A*0201 molecules. The CTL clones induced by SCRN1-9 V also recognized tumor cells expressing its natural SCRN1 protein endogenously. These results strongly suggest that SCRN1 is a novel TAA and these peptides, both native and modified, may be applicable for cancer vaccines to treat gastric cancer.
Insights
Researchers identified SCRN1 as a novel tumor-associated antigen (TAA) in gastric cancer. Peptides derived from SCRN1 successfully induced cytotoxic T lymphocytes (CTLs) capable of targeting cancer cells, suggesting potential for new cancer vaccines.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Limited clinical application of known tumor-associated antigens (TAAs) exists for epithelial malignancies.
- Novel TAAs are crucial for developing effective cancer immunotherapies.
Purpose of the Study:
- To identify and characterize novel TAAs in gastric cancer.
- To evaluate the potential of SCRN1-derived peptides as targets for cancer vaccines.
Main Methods:
- cDNA microarray analysis to screen for candidate TAAs in gastric cancer.
- Semiquantitative RT-PCR and Northern blot analysis to determine SCRN1 expression patterns.
- Colony formation assays to assess SCRN1's role in cell growth.
- Peptide synthesis and induction of cytotoxic T lymphocytes (CTLs) restricted to HLA-A*0201.
- In vitro assays to evaluate CTL-mediated tumor cell lysis.
Main Results:
- SCRN1 was identified as a candidate TAA, highly expressed in gastric cancer tissues but minimally in normal adult organs.
- Overexpression of SCRN1 correlated with enhanced cell growth.
- SCRN1-derived peptides (SCRN1-196 and modified SCRN1-9 V) successfully induced CTLs.
- Induced CTLs effectively lysed gastric cancer cells expressing SCRN1 and HLA-A*0201.
Conclusions:
- SCRN1 is a novel TAA with potential for gastric cancer treatment.
- SCRN1-derived peptides, both native and modified, show promise for developing targeted cancer vaccines.