Hiroshi Sawayama1, Yuji Miyamoto1, Kosuke Mima1, Rikako Kato1, Katsuhiro Ogawa1, Yukiharu Hiyoshi2, Mototsugu Shimokawa3, Takahiko Akiyama1, Yuki Kiyozumi3, Shiro Iwagami1, Masaaki Iwatsuki1, Yoshifumi Baba1, Naoya Yoshida1, Hideo Baba4. 1. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. 2. Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan. 3. Department of Biostatistics, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan. 4. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. hdobaba@kumamoto-u.ac.jp.
Abstract
BACKGROUND: Iron deficiency anemia is represented in colorectal cancer (CRC) patients. Iron surplus load to increase non-transferrin bound iron (NTBI), and NTBI promotes cancer progression and influences microbiota. This study investigated whether preoperative serum iron status was associated with prognosis after CRC resection. METHODS: We evaluated preoperative iron and transferrin saturation (TSAT), which was calculated as iron divided by total iron-binding capacity, in 327 patients who underwent surgery for Stage II-III CRC. Fe < 60 μg/dl and TSAT > 40% were defined as low and high iron, respectively. The associations between iron status and overall survival (OS) were evaluated in univariate and multivariate Cox proportional hazards analysis. RESULTS: Of the 327 patients, 179 (54.7%), 124 (37.9%) and 24 (7.3%) had low, normal and high iron, respectively. In univariate analysis, low iron was associated with shorter OS (hazard ratio [HR] 2.821, 95% confidence interval [CI] 1.451-5.485, P = 0.002). High iron was also associated with shorter OS (HR 3.396, 95% CI 1.359-8.489, P = 0.009). In multivariate analysis, high age (P = 0.002), depth of invasion pT4 (P = 0.012), lymph-node metastasis presence (P = 0.035), low albumin (P = 0.011), low iron (HR 2.282, 95% CI 1.163-4.478, P = 0.016) and high iron (HR 3.757, 95% CI 1.486-9.494 P = 0.005) were independently associated with shorter OS. High iron was associated with the amount of intratumoral Fusobacterium nucleatum compared with normal iron. CONCLUSION: Both low and high preoperative iron in Stage II-III CRC patients were associated with unfavorable OS in univariate and multivariate analyses.
BACKGROUND:Irondeficiency anemia is represented in colorectal cancer (CRC) patients. Iron surplus load to increase non-transferrin bound iron (NTBI), and NTBI promotes cancer progression and influences microbiota. This study investigated whether preoperative serum iron status was associated with prognosis after CRC resection. METHODS: We evaluated preoperative iron and transferrin saturation (TSAT), which was calculated as iron divided by total iron-binding capacity, in 327 patients who underwent surgery for Stage II-III CRC. Fe < 60 μg/dl and TSAT > 40% were defined as low and high iron, respectively. The associations between iron status and overall survival (OS) were evaluated in univariate and multivariate Cox proportional hazards analysis. RESULTS: Of the 327 patients, 179 (54.7%), 124 (37.9%) and 24 (7.3%) had low, normal and high iron, respectively. In univariate analysis, low iron was associated with shorter OS (hazard ratio [HR] 2.821, 95% confidence interval [CI] 1.451-5.485, P = 0.002). High iron was also associated with shorter OS (HR 3.396, 95% CI 1.359-8.489, P = 0.009). In multivariate analysis, high age (P = 0.002), depth of invasion pT4 (P = 0.012), lymph-node metastasis presence (P = 0.035), low albumin (P = 0.011), low iron (HR 2.282, 95% CI 1.163-4.478, P = 0.016) and high iron (HR 3.757, 95% CI 1.486-9.494 P = 0.005) were independently associated with shorter OS. High iron was associated with the amount of intratumoral Fusobacterium nucleatum compared with normal iron. CONCLUSION: Both low and high preoperative iron in Stage II-III CRCpatients were associated with unfavorable OS in univariate and multivariate analyses.
Authors: Kosuke Mima; Reiko Nishihara; Zhi Rong Qian; Yin Cao; Yasutaka Sukawa; Jonathan A Nowak; Juhong Yang; Ruoxu Dou; Yohei Masugi; Mingyang Song; Aleksandar D Kostic; Marios Giannakis; Susan Bullman; Danny A Milner; Hideo Baba; Edward L Giovannucci; Levi A Garraway; Gordon J Freeman; Glenn Dranoff; Wendy S Garrett; Curtis Huttenhower; Matthew Meyerson; Jeffrey A Meyerhardt; Andrew T Chan; Charles S Fuchs; Shuji Ogino Journal: Gut Date: 2015-08-26 Impact factor: 23.059
Authors: Raaj S Mehta; Reiko Nishihara; Yin Cao; Mingyang Song; Kosuke Mima; Zhi Rong Qian; Jonathan A Nowak; Keisuke Kosumi; Tsuyoshi Hamada; Yohei Masugi; Susan Bullman; David A Drew; Aleksandar D Kostic; Teresa T Fung; Wendy S Garrett; Curtis Huttenhower; Kana Wu; Jeffrey A Meyerhardt; Xuehong Zhang; Walter C Willett; Edward L Giovannucci; Charles S Fuchs; Andrew T Chan; Shuji Ogino Journal: JAMA Oncol Date: 2017-07-01 Impact factor: 31.777