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Wen-Zhuo He,1,* Qiu-Xia Yang,2,* Jin-Ye Xie,3,* Peng-Fei Kong,1 Wan-Ming Hu,4 Lin Yang,1 Yuan-Zhong Yang,4 Qian-Kun Xie,1 Chang Jiang,1 Chen-Xi Yin,1 Gui-Fang Guo,1 Hui-Juan Qiu,1 Bei Zhang,1 Liang-Ping Xia1 1VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China; 2Department of Medical Imaging, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China; 3Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510060, People’s Republic of China; 4Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China *These authors contributed equally to this work Background: Skeletal muscle depletion is a prognostic factor in patients with cancer. Here, we evaluated the association between the skeletal muscle index (SMI) and local and systemic responses in patients with colon cancer.Patients and methods: We analyzed the relationships of the SMI with neutrophil, lymphocyte, monocyte, and platelet counts; the neutrophil-to-lymphocyte ratio; albumin levels; and C-reactive protein levels in a cohort of 561 patients, and with the circulating levels of 39 cytokines in a cohort of 125 patients. We also studied the association between the SMI and tumor local inflammatory response and the effect of SMI on survival.Results: The median SMIs for male and female subjects were 44.1 and 34.2 cm2/m2, respectively. We observed positive correlations of the SMI with neutrophil (p=0.022), lymphocyte (p=0.001), and monocyte counts (p=0.003). A low SMI correlated significantly with an increased platelet count (p=0.017), decreased albumin level (p=0.006), neutrophil-to-lymphocyte ratio >3 (p=0.021), and an increased interferon γ-induced protein 10 level (IP-10, r = –0.276, p=0.002). The SMI did not correlate significantly with local inflammatory reactions or the C-reactive protein level. Finally, the SMI was a significant prognosticator in patients with stage III colon cancer (3-year disease-free survival rates: 35.1% for the low SMI arms versus 46.0% in the high SMI arms; HR =2.036; p=0.034).Conclusion: This study highlights the association of a low SMI with a high systematic inflammatory response and IP-10 levels. Furthermore, low SMI is a predictor of poor disease-free survival in patients with stage III colon cancer. Keywords: colon cancer, skeletal muscle, interferon γ-induced protein 10

Wen-Zhuo He,1,* Qian-Kun Xie,1,* Wan-Ming Hu,2–4,* Peng-fei Kong,1 Lin Yang,1 Yuan-Zhong Yang,2 Chang Jiang,1 Chen-Xi Yin,1 Hui-Juan Qiu,1 Hui-Zhong Zhang,2 Bei Zhang,1 Liang-Ping Xia1 1VIP Region, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: The purpose of the present study was to examine the relationship among the number of negative lymph nodes (LNs), the local and systemic immune response, and survival in patients with colon cancer. Patients and methods: One thousand one hundred and fifty-seven patients with colon cancer who underwent surgery at Sun Yat-sen University Cancer Center between 2009 and 2014 were included. We examined negative LNs in relation to the local and systemic immune response, including percentage carcinoma, neutrophil and lymphocyte infiltration, Crohn’s-like reaction, neutrophil to lymphocyte ratio, platelets, and C-reactive protein (CRP). Disease-free survival and overall survival were also examined. We performed subgroup analysis based on the distribution of negative LNs. Results: An increased number of negative LNs was associated with greater neutrophil invasion (p=0.001), more lymphocyte invasion (p=0.001), and more Crohn’s-like reaction (p=0.001). No significant correlation was observed between negative LNs and the neutrophil to lymphocyte ratio. More than 12 negative LNs were associated with increased platelets and CRP levels. A higher number of negative LNs was independently associated with longer disease-free survival in stage I+II patients (p=0.004) and stage III patients (p=0.015), while negative LNs were also independent prognostic factors in stage IV patients (p=0.007). Conclusion: Our study suggests that negative LNs are indicators of the immune response and are associated with a better prognosis in patients with colon cancer. Keywords: colon cancer, negative lymph nodes, immune response, survival