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体成分、炎症与结肠癌 5 年结局

Body Composition, Inflammation, and 5-Year Outcomes in Colon Cancer.

机构信息

Surguvant Research Centre, Cork University Hospital, Cork, Ireland.

Department of Colorectal Surgery, Cork University Hospital, Cork, Ireland.

出版信息

JAMA Netw Open. 2021 Aug 2;4(8):e2115274. doi: 10.1001/jamanetworkopen.2021.15274.

Abstract

IMPORTANCE

Obesity, particularly visceral obesity and sarcopenia, are poor prognostic indicators in colon cancer.

OBJECTIVES

To explore the association between body composition profiles and 5-year colon cancer outcomes and delineate the associated underlying inflammatory processes.

DESIGN, SETTING, AND PARTICIPANTS: 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.

EXPOSURE

Nonmetastatic colon cancer.

MAIN OUTCOMES AND MEASURES

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.

RESULTS

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).

CONCLUSIONS AND RELEVANCE

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.

摘要

重要性

肥胖,尤其是内脏肥胖和肌肉减少症,是结肠癌预后不良的指标。

目的

探讨体成分谱与 5 年结肠癌结局的关系,并阐明相关的潜在炎症过程。

设计、地点和参与者:本多中心转化队列研究纳入了 2009 年至 2015 年间来自三级癌症中心的无潜在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。检测了术前急性期蛋白(白细胞计数、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(CD11b 和 CD14)。所有患者均随访至少 5 年。数据于 2020 年 12 月进行分析。

暴露

非转移性结肠癌。

主要观察指标和测量方法

使用曼特尔 Cox 对数秩检验和 Kaplan-Meier 曲线分析体成分谱与 5 年癌症复发和疾病特异性死亡率的关系。

结果

共纳入 28 例患者(中位数[四分位间距]年龄,67[58-72]岁;22[78.6%]为男性)。低骨骼肌面积(SMA)和高内脏脂肪与总脂肪比与不良的临床和肿瘤学结局相关,包括增加 5 年复发(低 SMA:风险比[HR],2.30[95%CI,1.41-2.89];P=0.04;高内脏脂肪与总脂肪比:HR,5.78[95%CI,3.66-7.95];P=0.02)。高内脏脂肪与总脂肪比与 5 年疾病特异性死亡率增加相关(HR,5.92[95%CI,4.04-8.00];P=0.02)。与未复发的患者相比,发生癌症复发的低 SMA 患者的 C 反应蛋白(均值[标准差],31.24[6.95]mg/dL 比 8.11[0.58]mg/dL;P=0.003)、IL-6(均值[标准差],1.93[1.16]ng/mL 比 0.88[0.14]ng/mL;P=0.004)、VEGF(均值[标准差],310.03[122.66]ng/mL 比 176.12[22.94]ng/mL;P=0.007)和 CD14(均值[标准差],521.23[302.02]ng/mL 比 322.07[98.35]ng/mL;P=0.03)表达水平较高,而白蛋白(均值[标准差],3.8[0.6]g/dL 比 43.50[3.69]g/dL;P=0.01)、IL-2(均值[标准差],0.45[0.25]ng/mL 比 0.94[0.43]ng/mL;P<0.001)、IL-10(均值[标准差],8.15[1.09]ng/mL 比 16.32[4.43]ng/mL;P=0.004)和干扰素 γ(均值[标准差],2.61[1.36]ng/mL 比 14.87[3.43]ng/mL;P=0.02)水平较低。发生复发的高内脏脂肪与总脂肪比患者的 IL-6(均值[标准差],5.26[7.05]ng/mL 比 2.76[3.11]ng/mL;P=0.03)和肿瘤坏死因子 α(均值[标准差],5.74[4.53]ng/mL 比 4.50[1.99]ng/mL;P=0.03)水平较高。

结论和相关性

这些发现表明,低 SMA 和高内脏脂肪与总脂肪比与结肠癌结局较差相关,并与促炎细胞因子和 VEGF 表达增加以及抗炎细胞因子抑制相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d162/8406082/cd532bc11fc7/jamanetwopen-e2115274-g001.jpg

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