Revolutionizing Gastric Cancer: New Genetic Classification

Professor Sang Cheul Oh of the Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Professor Sang Hee Kang of the Department of Surgery, Korea University’s Guro Hospital, and Professor Sun Young Yim of the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine announced a new genetic classification system for gastric cancer as part of a multicenter study with the United Nations University. This study lay the groundwork for customized treatment of stomach cancer.

This multicenter study included five institutions: MD Anderson Cancer Center, Korea University College of Medicine, CHA University Medical Center, Kyung Hee University School of Medicine, Yonsei University College of Medicine, and Sungkyunkwan University School of Medicine. Professor JuSeog Lee of MD Anderson Cancer Center conducted the study, while Professor Sang Cheul Oh of the Division of Oncology/Hematology also took part. As co-lead authors, Professor SangHee Kang of the Department of Surgery and Professor Sun Young Yim of the Division of Gastroenterology and Hepatology contributed. The MD Anderson-Korea University research team previously published the genetic classification method for liver cancer in Hepatology (impact factor 17.3), a top-tier gastrointestinal journal.

Gastric cancer is distinguished by genetic and clinical variation. The researchers examined the gene classification scheme for eight previously published gastric tumors and came up with six Consensus Genomic Subtypes (CGSs). Based on distinct gene expression patterns, this system classified gastric tumors from CGS1 to CGS6.

Each subtype displayed unique characteristics, with CGS1 having the worst prognostic traits. It possessed exceptional stem cell characteristics and required little genetic alteration. The investigation did, however, reveal that CGS1 reacted well to immunotherapy and that medicines targeting IGF1R could be helpful. CGS2 was shown to be enriched in epithelial cell gene expression. CGS3 and CGS4 had substantial cloning number variation and poor immunotherapy responses. Nonetheless, CGS3 demonstrated HER2 gene activation and CGS4 demonstrated SALL4 gene activation. The team determined that treatments aimed at those characteristics would be beneficial. CGS5 had a high mutation burden, which is a sign of microsatellite instability in tumors, and responded moderately to immunotherapy.CGS6 had very high methylation levels and was predominantly positive for infectious mononucleosis (Epstein Barr) virus. It responded well to immunotherapy.

Through thorough analysis of genome and proteome data, the research team not only identified the genetics of stomach cancer, but also predicted the prospective response rates of standard and experimental treatments (chemoradiotherapy, immunotherapy, etc.) for each subtype. As a result of its iron-dependent cell death caused by large levels of lipid peroxidation, the CGS3 subtype demonstrated particularly significant benefits in anticancer radiation. For each subtype, research suggested suitable treatment subjects.

Professor Sun Young Yim of the Division of Gastroenterology and Hepatology, one of the lead authors of this study, said,

Although the mortality rate of gastric cancer is decreasing due to the implementation of new therapies, it still is one of the major causes of death for cancer patients. We believe that this research is going to lay the foundation for personalized gastric cancer treatments.”

I am a surgeon, but I am interested in new therapy beyond surgery. I’ll continue my best to conquer cancer in the future through convergence research.”

Professor Sang‑Hee Kang of Department of Surgery