Ho Seung Kim1, Kyeong Min Kim2, Sat Byol Lee1,3, Ga Ram Kim4, Yoon Dae Han1, Min Soo Cho1, Hyuk Hur1, Kang Young Lee1, Nam Kyu Kim1, Byung Soh Min1,3. 1. Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. 2. Department of Pathology, Yonsei University College of Medicine, Seoul, Korea. 3. Department of Surgery, Open NBI Convergence Technology Laboratory, Avison Biomedical Research Center, Yonsei University College of Medicine, Seoul, Korea. 4. Department of Radiology, Inha University Hospital, Inha University School of Medicine, Incheon, Korea.
Abstract
BACKGROUND: A survival paradox of stage IIB/IIC and IIIA colon cancer has been consistently observed throughout revisions of the TNM system. This study aimed to understand this paradox with clinicopathological and molecular differences. METHODS: Clinicopathological characteristics of patients with pathologically confirmed stage IIB/IIC or IIIA colon cancer were retrospectively reviewed from a database. Publicly available molecular data were retrieved, and intrinsic subtypes were identified and subjected to gene sets enrichment analysis (GSEA). RESULTS: Among the 159 patients included in the clinicopathological analysis, those at stage IIB/IIC had worse 3-year disease-free and overall survival than those at stage IIIA (59.3% vs 91.7%, P < 0.001 and 82.7% vs 98.5%, P < 0.001, respectively), even after adjusting for confounding factors. Data of 95 patients were retrieved from public databases, demonstrating a higher frequency of the microsatellite instable subtype in stage IIB/IIC. The consensus molecular subtype distribution pattern differed between the groups. The GSEA further suggested the protumor inflammatory reaction might be more prominent in stage IIB/IIC. CONCLUSIONS: The survival paradox in colon cancer was confirmed and appears to be a multifactorial phenomenon not attributed to a single clinicopathologic factor. However, the greater molecular heterogeneity in stage IIB/IIC could contribute to the poor prognosis.
BACKGROUND: A survival paradox of stage IIB/IIC and IIIA colon cancer has been consistently observed throughout revisions of the TNM system. This study aimed to understand this paradox with clinicopathological and molecular differences. METHODS: Clinicopathological characteristics of patients with pathologically confirmed stage IIB/IIC or IIIA colon cancer were retrospectively reviewed from a database. Publicly available molecular data were retrieved, and intrinsic subtypes were identified and subjected to gene sets enrichment analysis (GSEA). RESULTS: Among the 159 patients included in the clinicopathological analysis, those at stage IIB/IIC had worse 3-year disease-free and overall survival than those at stage IIIA (59.3% vs 91.7%, P < 0.001 and 82.7% vs 98.5%, P < 0.001, respectively), even after adjusting for confounding factors. Data of 95 patients were retrieved from public databases, demonstrating a higher frequency of the microsatellite instable subtype in stage IIB/IIC. The consensus molecular subtype distribution pattern differed between the groups. The GSEA further suggested the protumor inflammatory reaction might be more prominent in stage IIB/IIC. CONCLUSIONS: The survival paradox in colon cancer was confirmed and appears to be a multifactorial phenomenon not attributed to a single clinicopathologic factor. However, the greater molecular heterogeneity in stage IIB/IIC could contribute to the poor prognosis.