Deans D A C, Wigmore S J, Gilmour H, Paterson-Brown S, Ross J A, Fearon K C H
Tissue Injury and Repair Group, Department of Clinical and Surgical Sciences, MRC Centre for Inflammation Research, The Chancellor's Building, Edinburgh University, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
Br J Cancer. 2006 Dec 4;95(11):1568-75. doi: 10.1038/sj.bjc.6603446. Epub 2006 Nov 7.
Systemic inflammation is associated with adverse prognosis cancer but its aetiology remains unclear. We investigated the expression of proinflammatory cytokines within normal mucosa from healthy controls and tumour tissue in cancer patients and related these levels with markers of systemic inflammation and with the presence of a tumour inflammatory infiltrate. Tissue was collected from 56 patients with gastro-oesophageal cancer and from 12 healthy controls. Tissue cytokine mRNA concentrations were measured by real-time PCR and tissue protein concentrations by cytometric bead array. The degree of chronic inflammatory cell infiltrate was recorded. Serum cytokine and acute phase protein concentrations (including C-reactive protein (CRP)) were measured by enzyme-linked immunosorbent assay. Proinflammatory cytokines were significantly overexpressed (interleukin (IL)-1beta, IL-6, IL-8 and tumour necrosis factor-alpha) both at mRNA and protein levels in the cancer specimens compared with mucosa from controls. Interleukin-1beta was expressed in greatest (10-100-fold) concentration and protein levels correlated significantly with systemic inflammation (CRP) (P = 0.05, r = 0.31). A chronic inflammatory infiltrate was observed in 75% of the cancer specimens and was associated with systemic inflammation (CRP: P = 0.01). However, the presence of chronic inflammation per se was not associated with altered cytokine expression within the tumour. Both a chronic inflammatory infiltrate and systemic inflammation (CRP) were associated with reduced survival (P = 0.05 and P = 0.03, respectively). Tumour chronic inflammatory infiltrate and tumour tissue IL-1beta overexpression are potential independent factors influencing systemic inflammation in oesophagogastric cancer patients.
全身炎症与癌症的不良预后相关,但其病因仍不清楚。我们研究了健康对照者正常黏膜以及癌症患者肿瘤组织中促炎细胞因子的表达,并将这些水平与全身炎症标志物以及肿瘤炎性浸润的存在情况相关联。从56例胃食管癌患者和12例健康对照者中收集组织。通过实时聚合酶链反应测量组织细胞因子mRNA浓度,通过细胞计数珠阵列测量组织蛋白浓度。记录慢性炎性细胞浸润程度。通过酶联免疫吸附测定法测量血清细胞因子和急性期蛋白浓度(包括C反应蛋白(CRP))。与对照黏膜相比,癌症标本中促炎细胞因子(白细胞介素(IL)-1β、IL-6、IL-8和肿瘤坏死因子-α)在mRNA和蛋白水平均显著过表达。白细胞介素-1β以最高浓度(10至100倍)表达,蛋白水平与全身炎症(CRP)显著相关(P = 0.05,r = 0.31)。在75%的癌症标本中观察到慢性炎性浸润,且与全身炎症(CRP:P = 0.01)相关。然而,慢性炎症本身的存在与肿瘤内细胞因子表达改变无关。慢性炎性浸润和全身炎症(CRP)均与生存率降低相关(分别为P = 0.05和P = 0.03)。肿瘤慢性炎性浸润和肿瘤组织白细胞介素-1β过表达是影响食管胃癌患者全身炎症的潜在独立因素。