Body Composition, Inflammation, and 5-Year Outcomes in Colon Cancer.
Body Composition, Inflammation, and 5-Year Outcomes in Colon Cancer.
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DOI：
10.1001/jamanetworkopen.2021.15274
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发表时间：
2021-08-02
影响因子：
13.8
通讯作者：
Redmond HP
中科院分区：
文献类型：
--
作者：
Fleming CA;O'Connell EP;Kavanagh RG;O'Leary DP;Twomey M;Corrigan MA;Wang JH;Maher MM;O'Connor OJ;Redmond HP
潜在的炎症途径和身体成分与结肠癌5年预后不良相关吗？在这项包括28名非转移性结肠癌患者的队列研究中，高内脏脂肪和低肌肉质量与炎症活动增加和5年癌症预后不良相关，包括复发和疾病特异性死亡率。低骨骼肌面积和高内脏脂肪占总脂肪的比例与促炎细胞因子和血管内皮生长因子表达增加以及5年癌症预后较差的患者中保护性抑制细胞因子的抑制有关。这些发现表明，与低骨骼肌面积和高内脏总脂肪比相关的结肠癌预后不良也与促炎细胞因子和血管内皮生长因子表达增加以及保护性抑制细胞因子水平降低相关。这项队列研究探讨了身体成分、炎症标志物表达和5年结肠癌预后之间的关系。肥胖，特别是内脏肥胖和肌肉减少症，是结肠癌的不良预后指标。探讨身体成分与5年结肠癌预后之间的关系，并描述相关的潜在炎症过程。这项多中心转化队列研究纳入了2009年至2015年期间转诊至三级癌症中心的无基础慢性炎症性疾病且未接受抗炎药物治疗的非转移性结肠癌患者。测量术前急性期蛋白（白色细胞计数、C反应蛋白和白蛋白）、细胞因子（白细胞介素[IL]-1b、IL-2、IL-6、IL-10、干扰素γ和肿瘤坏死因子α）、血管内皮生长因子（VEGF）和细胞表面受体表达水平（CD 11b和CD 14）。所有患者均接受了至少5年的随访。数据于2020年12月进行分析。非转移性结肠癌。采用Mantel考克斯log-rank检验和Kaplan-Meier曲线分析身体成分与5年癌症复发和疾病特异性死亡率的关系。共纳入28例患者（中位[四分位距]年龄：67 [58-72]岁; 22例[78.6%]男性）。低骨骼肌面积（SMA）和高内脏脂肪/总脂肪比与临床和肿瘤结局不良相关，包括5年复发率增加（低SMA：风险比[HR]，2.30 [95% CI，1.41-2.89]; P = 0.04;高内脏脂肪/总脂肪比：HR，5.78 [95% CI，3.66-7.95]; P = 0.02）。高内脏脂肪/总脂肪比与5年疾病特异性死亡率增加相关（HR，5.92 [95% CI，4.04-8.00]; P = .02）。与那些没有发生癌症复发的患者相比，低SMA患者的C反应蛋白水平较高（平均值[SD]，31.24 [6.95] mg/dL vs 8.11 [0.58] mg/dL; P = .003），IL-6（平均值[SD]，1.93 [1.16] ng/mL vs 0.88 [0.14] ng/mL; P = .004），VEGF（平均值[SD]，310.03 [122.66] ng/mL vs 176.12 [22.94] ng/mL; P = 0.007）和CD 14（平均值[SD]，521.23 [302.02] ng/mL vs 322.07 [98.35] ng/mL; P = .03）表达和低白蛋白（平均值[SD]，3.8 [0.6] g/dL vs 43.50 [3.69] g/dL; P = .01），IL-2（平均值[SD]，0.45 [0.25] ng/mL vs 0.94 [0.43] ng/mL; P < .001），IL-10（平均值[SD]，8.15 [1.09] ng/mL vs 16.32 [4.43] ng/mL; P = .004）和干扰素γ（平均值[SD]，2.61 [1.36] ng/mL vs 14.87 [3.43] ng/mL; P = .02）水平。内脏脂肪与总脂肪比例高的患者复发时IL-6水平较高（平均值[SD]，5.26 [7.05] ng/mL vs 2.76 [3.11] ng/mL; P = 0.03），肿瘤坏死因子α水平较高（平均值[SD]，5.74 [4.53] ng/mL vs 4.50 [1.99] ng/mL; P = 0.03）。这些结果表明，低SMA和高内脏脂肪与总脂肪的比例与结肠癌的预后较差相关，并与促炎细胞因子和VEGF的表达增加以及抗炎细胞因子的抑制相关。
Are underlying inflammatory pathways and body composition profiles associated with less favorable 5-year colon cancer outcomes? In this cohort study including 28 patients with nonmetastatic colon cancer, high visceral fat and low muscle mass were associated with increased inflammatory activity and poor 5-year cancer outcomes, including recurrence and disease-specific mortality. Low skeletal muscle area and high visceral to total fat ratio were associated with increased expression of proinflammatory cytokines and vascular endothelial growth factor and inhibition of protective inhibitory cytokines in patients with less favorable 5-year cancer outcomes. These findings suggest that less favorable colon cancer outcomes associated with low skeletal muscle area and high visceral to total fat ratio were also associated with increased expression of proinflammatory cytokines and vascular endothelial growth factor and lower levels of protective inhibitory cytokines. This cohort study examines associations among body composition profiles, inflammatory marker expressions, and 5-year colon cancer outcomes. Obesity, particularly visceral obesity and sarcopenia, are poor prognostic indicators in colon cancer. To explore the association between body composition profiles and 5-year colon cancer outcomes and delineate the associated underlying inflammatory processes. This multicenter translational cohort study included patients with nonmetastatic colon cancer who did not have underlying chronic inflammatory disorders and were not receiving anti-inflammatory drugs referred to tertiary cancer centers from 2009 to 2015. Preoperative acute phase proteins (white cell count, C-reactive protein, and albumin), cytokines (interleukin [IL]-1b, IL-2, IL-6, IL-10, interferon γ, and tumor necrosis factor α), vascular endothelial growth factor (VEGF), and cell surface receptor expression levels (CD11b and CD14) were measured. All patients underwent follow-up for at least 5 years. Data were analyzed in December 2020. Nonmetastatic colon cancer. The associations of body composition profiles with 5-year cancer recurrence and disease-specific mortality were analyzed using Mantel Cox log-rank test and Kaplan-Meier curves. A total of 28 patients were included (median [interquartile range] age, 67 [58-72] years; 22 [78.6%] men). Low skeletal muscle area (SMA) and high visceral to total fat ratio were associated with poor clinical and oncological outcomes, including increased 5-year recurrence (low SMA: hazard ratio [HR], 2.30 [95% CI, 1.41-2.89]; P = .04; high visceral to total fat ratio: HR, 5.78 [95% CI, 3.66-7.95]; P = .02). High visceral to total fat ratio was associated with increased 5-year disease-specific mortality (HR, 5.92 [95% CI, 4.04-8.00]; P = .02). Patients with low SMA who developed a cancer recurrence, compared with those who did not, had higher C-reactive protein (mean [SD], 31.24 [6.95] mg/dL vs 8.11 [0.58] mg/dL; P = .003), IL-6 (mean [SD], 1.93 [1.16] ng/mL vs 0.88 [0.14] ng/mL; P = .004), VEGF (mean [SD], 310.03 [122.66] ng/mL vs 176.12 [22.94] ng/mL; P = .007), and CD14 (mean [SD], 521.23 [302.02] ng/mL vs 322.07 [98.35] ng/mL; P = .03) expression and lower albumin (mean [SD], 3.8 [0.6] g/dL vs 43.50 [3.69] g/dL; P = .01), IL-2 (mean [SD], 0.45 [0.25] ng/mL vs 0.94 [0.43] ng/mL; P < .001), IL-10 (mean [SD], 8.15 [1.09] ng/mL vs 16.32 [4.43] ng/mL; P = .004), and interferon γ (mean [SD], 2.61 [1.36] ng/mL vs 14.87 [3.43] ng/mL; P = .02) levels. Patients with high visceral to total fat ratio who developed recurrence had higher levels of IL-6 (mean [SD], 5.26 [7.05] ng/mL vs 2.76 [3.11] ng/mL; P = .03) and tumor necrosis factor α (mean [SD], 5.74 [4.53] ng/mL vs 4.50 [1.99] ng/mL; P = .03). These findings suggest that low SMA and high visceral to total fat ratio were associated with worse colon cancer outcomes and with increased expression of proinflammatory cytokines and VEGF and inhibition of anti-inflammatory cytokines.
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DOI：
10.1002/jcsm.12234
发表时间：
2018-03
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Choi MH;Oh SN;Lee IK;Oh ST;Won DD
通讯作者：
Won DD
影响因子：
2.5
作者：
Ballian, Nikiforos;Lubner, Meghan G.;Kennedy, Gregory D.
通讯作者：
Kennedy, Gregory D.
影响因子：
7
作者：
Doyle, Suzanne L.;Donohoe, Claire L.;Reynolds, John V.
通讯作者：
Reynolds, John V.
影响因子：
3.1
作者：
Bye, Asta;Jordhoy, Marit S.;Hjermstad, Marianne Jensen
通讯作者：
Hjermstad, Marianne Jensen
影响因子：
9.6
作者：
Ishii, Y;Hasegawa, H;Kitajima, M
通讯作者：
Kitajima, M