Duvillard Laurence, Ortega-Deballon Pablo, Bourredjem Abderrahmane, Scherrer Marie-Lorraine, Mantion Georges, Delhorme Jean-Baptiste, Deguelte-Lardière Sophie, Petit Jean-Michel, Bonithon-Kopp Claire
Inserm UMR 866, Faculté de médecine de Dijon, Dijon 21079-F, France.
BMC Cancer. 2014 Dec 3;14:912. doi: 10.1186/1471-2407-14-912.
Chronic inflammation is a key feature of colorectal cancer (CRC), meaning that inflammatory biomarkers may be useful for its diagnosis. In particular, high neutrophil gelatinase-associated lipocalin (NGAL) expression has been reported in CRC. Thus, we investigated whether serum NGAL and NGAL/MMP-9 could be potential biomarkers for the early detection of CRC. Concurrently, we studied other inflammatory biomarkers such as soluble tumor necrosis factor receptor 1 and 2 (sTNFR-1, sTNFR-2), and C reactive protein (CRP).
The AGARIC multicenter case-control study was performed in eastern France and included patients admitted for elective surgery either for a priori non-metastatic incident CRC (n=224) or for benign causes (n=252). Pre-operative serum levels of NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were measured.
Median values of serum NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were significantly higher in CRC patients than in controls. Receiver Operating Characteristic analysis provided relatively poor values of area under the curve, ranging from 0.65 to 0.58. Except for NGAL/MMP-9, all biological parameters were strongly correlated in CRC cases and, less strongly in controls. Multivariate odds ratio (OR) of CRC comparing the extreme tertiles of serum NGAL was 2.76 (95% confidence interval (CI): 1.59-4.78; p<0.001),. Lower but significant multivariate associations were observed for sTNFR-1, and sTNFR-2: OR=2.44 (95% CI : 1.34-4.45, p=0.015) and 1.93 (95% : CI 1.12-3.31), respectively. No independent association was found between case-control status and NGAL/MMP-9. Among CRC cases, maximal tumor size was an independent determinant of serum NGAL (p=0.028) but this association was reduced after adjustment for CRP (p=0.11).
Despite a significant increase in serum NGAL and other inflammatory markers among CRC patients, our findings suggest that they may not be suitable biomarkers for the diagnosis and especially early detection of CRC.
慢性炎症是结直肠癌（CRC）的一个关键特征，这意味着炎症生物标志物可能有助于其诊断。特别是，已有报道称结直肠癌中嗜中性粒细胞明胶酶相关脂质运载蛋白（NGAL）表达较高。因此，我们研究了血清NGAL和NGAL/MMP-9是否可能是结直肠癌早期检测的潜在生物标志物。同时，我们还研究了其他炎症生物标志物，如可溶性肿瘤坏死因子受体1和2（sTNFR-1、sTNFR-2）以及C反应蛋白（CRP）。
AGARIC多中心病例对照研究在法国东部进行，纳入了因择期手术入院的患者，其中包括因先验非转移性初发结直肠癌（n=224）或良性病因（n=252）入院的患者。测量术前血清中NGAL、NGAL/MMP-9、sTNFR-1、sTNFR-2和CRP的水平。
结直肠癌患者血清NGAL、NGAL/MMP-9、sTNFR-1、sTNFR-2和CRP的中位数显著高于对照组。受试者工作特征分析得出的曲线下面积值相对较差，范围在0.65至0.58之间。除NGAL/MMP-9外，所有生物学参数在结直肠癌病例中相关性较强，在对照组中相关性较弱。比较血清NGAL最高和最低三分位数时，结直肠癌的多变量优势比（OR）为2.76（95%置信区间（CI）：1.59-4.78；p<0.001）。sTNFR-1和sTNFR-2的多变量关联较低但具有显著性：OR分别为2.44（95%CI：1.34-4.45，p=0.015）和1.93（95%CI：1.12-3.31）。未发现病例对照状态与NGAL/MMP-9之间存在独立关联。在结直肠癌病例中，最大肿瘤大小是血清NGAL的一个独立决定因素（p=0.028），但在调整CRP后这种关联减弱（p=0.11）。
尽管结直肠癌患者血清NGAL和其他炎症标志物显著升高，但我们的研究结果表明，它们可能不是结直肠癌诊断尤其是早期检测的合适生物标志物。
