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Updated: Jun 25, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Transcriptome dissection of gastric cancer: identification of novel diagnostic and therapeutic targets from pathology
Wataru Yasui1, Naohide Oue, Kazuhiro Sentani
1Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. wyasui@hiroshima-u.ac.jp
Abstract:
Gastric cancer is the fourth most common malignancy in the world, and mortality due to gastric cancer is second only to that from lung cancer. 'Transcriptome dissection' is a detailed analysis of the entire expressed transcripts from a cancer, for the purpose of understanding the precise molecular mechanism of pathogenesis. Serial analysis of gene expression (SAGE) is a suitable technique for performing transcriptome dissection. Gastric cancers of different stages and histology were analyzed on SAGE, and one of the largest gastric cancer SAGE libraries in the world was created (GEO accession number GSE 545). Through SAGE, many candidate genes have been identified as potential diagnostic and therapeutic targets for the treatment of gastric cancer. Regenerating islet-derived family, member 4 (Reg IV) participated in 5-fluorouracil (5-FU) resistance and peritoneal metastasis, and its expression was associated with an intestinal phenotype of gastric cancer and with endocrine differentiation. GW112 expression correlated with advanced tumor stage. Measurement of Reg IV and GW112 levels in sera indicated a sensitivity of 57% for detection of cancer. SPC18 participated in tumor growth and invasion through transforming tumor growth factor-alpha upregulation. Palate, lung, and nasal epithelium carcinoma-associated protein (PLUNC) was a useful marker for gastric hepatoid adenocarcinoma. Expression of SOX9, HOXA10, CDH17, and loss of claudin-18 expression were associated with an intestinal phenotype of gastric cancer. Information obtained from transcriptome dissection greatly contributes to diagnosis and treatment of gastric cancer.
Insights
Transcriptome dissection using Serial Analysis of Gene Expression (SAGE) identified key genes in gastric cancer. These findings offer potential new diagnostic and therapeutic targets for this common malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Gastric cancer is a leading cause of cancer mortality worldwide.
- Understanding the molecular mechanisms of gastric cancer pathogenesis is crucial for effective treatment.
- Transcriptome dissection provides a comprehensive view of gene expression in cancer.
Purpose of the Study:
- To perform transcriptome dissection of gastric cancers using Serial Analysis of Gene Expression (SAGE).
- To identify novel diagnostic and therapeutic targets for gastric cancer.
- To correlate gene expression patterns with clinicopathological features and treatment resistance.
Main Methods:
- Serial Analysis of Gene Expression (SAGE) was employed to analyze transcripts from gastric cancers.
- A large-scale gastric cancer SAGE library was established (GEO accession number GSE 545).
- Gene expression data was correlated with tumor stage, histology, and patient outcomes.
Main Results:
- Regenerating islet-derived family, member 4 (Reg IV) was linked to 5-fluorouracil resistance and peritoneal metastasis.
- GW112 expression correlated with advanced tumor stage, and Reg IV/GW112 serum levels showed 57% sensitivity for cancer detection.
- Specific genes (SOX9, HOXA10, CDH17, claudin-18) were associated with intestinal phenotype, and PLUNC was a marker for gastric hepatoid adenocarcinoma.
Conclusions:
- Transcriptome dissection via SAGE has identified significant candidate genes for gastric cancer diagnosis and therapy.
- Reg IV, GW112, SPC18, PLUNC, SOX9, HOXA10, CDH17, and claudin-18 are implicated in gastric cancer progression and characteristics.
- This approach significantly advances the understanding and potential management of gastric cancer.
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