结直肠癌患者血清中性粒细胞明胶酶相关载脂蛋白检测的临床意义  

Clinical significance of the detection of serum neutrophii gelatinase-associated lipocalin in human colorectal cancer

作　　者：丁磊[1] 张秀峰[1] 张延祥[1] 杨关根[1] 廖秀军[1] 沈忠[1] 裘建明[1] 茅伟明[1] 胡莉桦 邵书先[1] 商善良 

机构地区：[1]安徽医科大学杭州临床学院(杭州市第三人民医院)普通外科,310009

出　　处：《中华胃肠外科杂志》2014年第6期589-593,共5页Chinese Journal of Gastrointestinal Surgery

基　　金：国家自然科学基金青年项目（81101876/H1617）;浙江省医药卫生平台骨于人才项目（2011RCA035）;浙江省卫生厅卫生平台骨干人才计划（2013RCB013）;浙江省科技厅公益技术研究社会发展项目（2012C33SA100045）;杭州市医学重点专科专病项目（20130733Q22）

摘　　要：目的探讨结直肠肿瘤患者血清中性粒细胞明胶酶相关载脂蛋白（NGAL）检测的临床意义。方法收集杭州市第三人民医院2007年12月至2012年12月间100例结直肠癌、125例结直肠腺瘤和133例健康志愿者的血清标本，通过双抗体夹心酶联免疫吸附试验检测血清NGAL水平。分析血清NGAL水平与结直肠癌临床病理特征的关系；通过受试者工作特征曲线分析确定血清NGAL诊断结直肠癌的最佳截点值，并与血清CEA和CA19—9的诊断价值进行比较。通过单因素和多因素预后分析，明确血清NGAL水平与结直肠癌患者预后的关系。结果结直肠癌患者血清NGAL水平中位数为67．96μg／L，明显高于结直肠腺瘤患者（32．09μg／L）和健康对照者（23．33μg／L）（均P〈0．01）。血清NGAL水平与结直肠癌分化程度、TNM分期、淋巴结转移及脉管侵犯有关（均P〈0．05）。取49．78μg／L作为血清NGAL诊断结直肠癌的最佳截点值，其灵敏度为81％，特异度为88％。对于Ⅰ期和Ⅱ期结肠癌患者，血清NGAL的灵敏度（78．9％和88．0％）高于CA19．9（31．6％和48．0％）和CEA（36．8％和52．0％），差异均有统计学意义（均P〈0．05）。NGAL阳性和阴性患者术后生存期中位数分别为13月和42月，差异有统计学意义（P〈0．05）。多因素预后分析证实，血清NGAL可作为结直肠癌患者的独立预后因素（HR=2．060，95％CI：1．023～4．150，P=0．043）。结论血清NGAL可作为结直肠癌的早期诊断标记物，同时可作为恶性生物表型标记用于结直肠癌的危险度评估，筛选高危患者，其表达上调提示不良预后。Objective To explore the feasibility and clinical significance of the detection of serum neutrophil gelatinase-associated lipocalin（NGAL） in human colorectal cancer. Methods Levels of NGAL in serum samples from 133 healthy people, 125 colorectal polyps patients and 100 colorectal cancer patients respectively were determined by sandwich ELISA assay. Relationship of NGAL level with clinicopathological features of colorectal cancer patients was analyzed. The optimal cut-off value of serum NGAL for diagnosing colorectal cancer was determined by ROC curve and compared with CEA and CA19-9. Univariate and multivariate analyses were performed to examine the relationship of NGAL level with the prognosis of patients with colorectal cancer. Results The median serum NGAL protein level in 100 colorectal cancer cases was 67.96（53.30-79.86） μg/L, significantly higher than that in healthy people and colorectal polyps patients. The differences were statistically significant （all P〈0.01）. Serum NGAL protein level was significantly associated with tumor diameter, TNM stage, lymph node metastasis and vascular involvement （P〈0.05）. The optimal cut-off point of serum NGAL protein level for diagnosing colorectal cancer was 49.78 μg/L, and the sensitivity and specificity were 88% and 81% respectively. As for colorectal cancer patients with stage I , the sensitivity of serum NGAL （78.9%） was significantly higher as compared to CA19-9 （31.6%） and CEA （36.8%）; as for those with stage I1 , the sensitivity of serum NGAL （88.0%） was also significantly higher compared to CA19-9 （48.0%） and CEA （52.0%）. Kaplan-Meier analysis showed that patients with positive NGAL （349.78 μg,/L） had worse survival than those with negative NGAL （P=0.002）. Multivariate analysis showed that NGAL was an independent prognostic factor （HR=2.060, 95%CI： 1.023-4.150, P=-0.043）. Conclusions NGAL can be served as the novel malignant biological phenotype marker for human colorectal cancer and can be used for the

关 键 词：结直肠肿瘤 中性粒细胞明胶酶相关载脂蛋白 早期诊断 预后标记物 

分 类 号：R735.34[医药卫生—肿瘤]