Eiji Shinto1, Eiji Oki2, Mototsugu Shimokawa3, Shigeki Yamaguchi4, Megumi Ishiguro5, Masaru Morita6, Tetsuya Kusumoto7, Naohiro Tomita8, Yojiro Hashiguchi9, Masafumi Tanaka10, Shinobu Ohnuma11, Sachiyo Tada12, Tomoko Matsushima12, Kazuo Hase13. 1. Department of Surgery, National Defense Medical College, Tokorozawa, Japan, shinto@ndmc.ac.jp. 2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 3. Clinical Research Institute, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 4. Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Japan. 5. Department of Translational Oncology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan. 6. Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 7. Department of Gastroenterological Surgery, Clinical Research Center, Cancer Research Division, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan. 8. Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan. 9. Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan. 10. Coloproctology Center, Takano Hospital, Kumamoto, Japan. 11. Department of Surgery, Tohoku University Hospital, Sendai, Japan. 12. LS Business, Sysmex Corporation, Kobe, Japan. 13. Department of Surgery, National Defense Medical College, Tokorozawa, Japan.
Abstract
INTRODUCTION: DNA microarrays, such as the consensus molecular subtype (CMS) classification using >600 genes, are used to predict cancer patient prognosis. We recently constructed a simple 55-gene classifier (55GC) system to risk stratify colon cancer (CC). OBJECTIVE: Here, we validate the 55GC specifically for stage II CC and compare it with CMS categories. METHODS: Tissue sections from 232 stage II CC patients who underwent curative surgery without adjuvant chemotherapy between 2009 and 2012 were subjected to DNA microarray analysis. RESULTS: Based on the 55GC, patients were classified into microsatellite instability-like (27%), chromosomal instability-like (41%), and stromal (32%) subtypes with 5-year relapse-free survival (RFS) rates of 88.5, 83.3, and 71.2%, respectively (stromal vs. others: p = 0.0049). Multivariate analysis by Cox's proportional hazard model revealed that the stromal subtype, pT4, and the number of lymph nodes examined (<12) were independent poor prognostic factors. The overall concordance rate between 55GC and CMS was 72%, and 5-year RFS rates of patients with CMS1, CMS2, CMS3, and CMS4 cancers were 100, 85.5, 92.3, and 73.0%, respectively (p = 0.0113). CONCLUSIONS: We conclude that the 55GC is a useful and reproducible grading system for stage II CC recurrence risk stratification.
INTRODUCTION: DNA microarrays, such as the consensus molecular subtype (CMS) classification using >600 genes, are used to predict cancerpatient prognosis. We recently constructed a simple 55-gene classifier (55GC) system to risk stratify colon cancer (CC). OBJECTIVE: Here, we validate the 55GC specifically for stage II CC and compare it with CMS categories. METHODS: Tissue sections from 232 stage II CCpatients who underwent curative surgery without adjuvant chemotherapy between 2009 and 2012 were subjected to DNA microarray analysis. RESULTS: Based on the 55GC, patients were classified into microsatellite instability-like (27%), chromosomal instability-like (41%), and stromal (32%) subtypes with 5-year relapse-free survival (RFS) rates of 88.5, 83.3, and 71.2%, respectively (stromal vs. others: p = 0.0049). Multivariate analysis by Cox's proportional hazard model revealed that the stromal subtype, pT4, and the number of lymph nodes examined (<12) were independent poor prognostic factors. The overall concordance rate between 55GC and CMS was 72%, and 5-year RFS rates of patients with CMS1, CMS2, CMS3, and CMS4 cancers were 100, 85.5, 92.3, and 73.0%, respectively (p = 0.0113). CONCLUSIONS: We conclude that the 55GC is a useful and reproducible grading system for stage II CC recurrence risk stratification.