Kenichiro Furukawa1,2, Keiichi Hatakeyama3, Masanori Terashima4, Takeshi Nagashima5,6, Kenichi Urakami5, Keiichi Ohshima3, Akifumi Notsu7, Takashi Sugino8, Taisuke Yagi1, Keiichi Fujiya1, Satoshi Kamiya1, Makoto Hikage1, Yutaka Tanizawa1, Etsuro Bando1, Yae Kanai2, Yasuto Akiyama9, Ken Yamaguchi10. 1. Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. 2. Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan. 3. Medical Genetics Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. 4. Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. m.terashima@scchr.jp. 5. Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. 6. SRL Inc., Shinjuku Mitsui Building, 2-1-1 Nishishinjuku, Shinjuku, Tokyo, 163-0403, Japan. 7. Clinical Research Center, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo,Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. 8. Division of Pathology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. 9. Immunotheraphy Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. 10. Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
Abstract
BACKGROUND: Gastric cancer (GC) has been classified based on molecular profiling like The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG), and attempts have been made to establish therapeutic strategies based on these classifications. However, it is difficult to predict the survival according to these classifications especially in radically resected patients. We aimed to establish a new molecular classification of GC which predicts the survival in patients undergoing radical gastrectomy. METHODS: The present study included 499 Japanese patients with advanced GC undergoing radical (R0/R1) gastrectomy. Whole-exome sequencing, panel sequencing, and gene expression profiling were conducted (High-tech Omics-based Patient Evaluation [Project HOPE]). We classified patients according to TCGA and ACRG subtypes, and evaluated the clinicopathologic features and survival. Then, we attempted to classify patients according to their molecular profiles associated with biological features and survival (HOPE classification). RESULTS: TCGA and ACRG classifications failed to predict the survival. In HOPE classification, hypermutated (HMT) tumors were selected first as a distinctive feature, and T-cell-inflamed expression signature-high (TCI) tumors were then extracted. Finally, the remaining tumors were divided by the epithelial-mesenchymal transition (EMT) expression signature. HOPE classification significantly predicted the disease-specific and overall survival (p < 0.001 and 0.020, respectively). HMT + TCI showed the best survival, while EMT-high showed the worst survival. The HOPE classification was successfully validated in the TCGA cohort. CONCLUSIONS: We established a new molecular classification of gastric cancer that predicts the survival in patients undergoing radical surgery.
BACKGROUND: Gastric cancer (GC) has been classified based on molecular profiling like The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG), and attempts have been made to establish therapeutic strategies based on these classifications. However, it is difficult to predict the survival according to these classifications especially in radically resected patients. We aimed to establish a new molecular classification of GC which predicts the survival in patients undergoing radical gastrectomy. METHODS: The present study included 499 Japanese patients with advanced GC undergoing radical (R0/R1) gastrectomy. Whole-exome sequencing, panel sequencing, and gene expression profiling were conducted (High-tech Omics-based Patient Evaluation [Project HOPE]). We classified patients according to TCGA and ACRG subtypes, and evaluated the clinicopathologic features and survival. Then, we attempted to classify patients according to their molecular profiles associated with biological features and survival (HOPE classification). RESULTS: TCGA and ACRG classifications failed to predict the survival. In HOPE classification, hypermutated (HMT) tumors were selected first as a distinctive feature, and T-cell-inflamed expression signature-high (TCI) tumors were then extracted. Finally, the remaining tumors were divided by the epithelial-mesenchymal transition (EMT) expression signature. HOPE classification significantly predicted the disease-specific and overall survival (p < 0.001 and 0.020, respectively). HMT + TCI showed the best survival, while EMT-high showed the worst survival. The HOPE classification was successfully validated in the TCGA cohort. CONCLUSIONS: We established a new molecular classification of gastric cancer that predicts the survival in patients undergoing radical surgery.
Authors: G Tamura; K Sakata; C Maesawa; Y Suzuki; M Terashima; K Satoh; S Sekiyama; A Suzuki; Y Eda; R Satodate Journal: Cancer Res Date: 1995-05-01 Impact factor: 12.701
Authors: Magdalena Koczkowska; Tom Callens; Yunjia Chen; Alicia Gomes; Alesha D Hicks; Angela Sharp; Eric Johns; Kim Armfield Uhas; Linlea Armstrong; Katherine Armstrong Bosanko; Dusica Babovic-Vuksanovic; Laura Baker; Donald G Basel; Mario Bengala; James T Bennett; Chelsea Chambers; Lola K Clarkson; Maurizio Clementi; Fanny M Cortés; Mitch Cunningham; M Daniela D'Agostino; Martin B Delatycki; Maria C Digilio; Laura Dosa; Silvia Esposito; Stephanie Fox; Mary-Louise Freckmann; Christine Fauth; Teresa Giugliano; Sandra Giustini; Allison Goetsch; Yael Goldberg; Robert S Greenwood; Cristin Griffis; Karen W Gripp; Punita Gupta; Eric Haan; Rachel K Hachen; Tamara L Haygarth; Concepción Hernández-Chico; Katelyn Hodge; Robert J Hopkin; Louanne Hudgins; Sandra Janssens; Kory Keller; Geraldine Kelly-Mancuso; Aaina Kochhar; Bruce R Korf; Andrea M Lewis; Jan Liebelt; Angie Lichty; Robert H Listernick; Michael J Lyons; Isabelle Maystadt; Mayra Martinez Ojeda; Carey McDougall; Lesley K McGregor; Daniela Melis; Nancy Mendelsohn; Malgorzata J M Nowaczyk; June Ortenberg; Karin Panzer; John G Pappas; Mary Ella Pierpont; Giulio Piluso; Valentina Pinna; Eniko K Pivnick; Dinel A Pond; Cynthia M Powell; Caleb Rogers; Noa Ruhrman Shahar; S Lane Rutledge; Veronica Saletti; Sarah A Sandaradura; Claudia Santoro; Ulrich A Schatz; Allison Schreiber; Daryl A Scott; Elizabeth A Sellars; Ruth Sheffer; Elizabeth Siqveland; John M Slopis; Rosemarie Smith; Alberto Spalice; David W Stockton; Haley Streff; Amy Theos; Gail E Tomlinson; Grace Tran; Pamela L Trapane; Eva Trevisson; Nicole J Ullrich; Jenneke Van den Ende; Samantha A Schrier Vergano; Stephanie E Wallace; Michael F Wangler; David D Weaver; Kaleb H Yohay; Elaine Zackai; Jonathan Zonana; Vickie Zurcher; Kathleen B M Claes; Marica Eoli; Yolanda Martin; Katharina Wimmer; Alessandro De Luca; Eric Legius; Ludwine M Messiaen Journal: Hum Mutat Date: 2019-10-26 Impact factor: 4.878