食管上皮不典型增生和早期癌血清标志物的初步研究

Serum Markers as Predictors of Esophageal Squamous Dysplasia and Early Cancer

目的寻找筛查食管鳞状上皮细胞癌前病变的方法,为食管癌的早期诊断提供依据。方法在河南省林州市食管癌高发区,使用食管镜和Lugol氏碘液染色检查对725人进行筛查研究。所有研究对象,取组织活检,并收集血样。按食管镜病理组织学结果分为正常、食管炎、不典型增生、早期癌,随机抽取84例作为研究对象,用ELISA方法检测血清中部分肿瘤分子标记物的浓度,包括:金属基质蛋白(MMP9);组织抑制因子(TIMP1);Cu/Zn过氧化物歧化酶(Cu/ZnSOD);抗p53自身抗体(Antip53autoantibody)和可溶血清白细胞2受体(IL2sRα)。结果正常和食管炎组MMP9浓度中位数为150ng/ml,四分位距为(80～225)ng/ml;不典型增生和早期癌组中位数为97ng/ml,四分位距为(58～155)ng/ml;两组间浓度差异有统计学意义(P=0.033)。其他4种血清标志物在两组间差异无统计学意义。结论MMP9检测对食管鳞状上皮不典型增生筛查有一定意义,但需要进一步研究。

Objective Squamous dysplasia is the precursor lesion for esophageal squamous cell carcinoma （ESCC）. A primary screening test for ESCC which identified this lesion could lead to a reduction in disease-specific mortality and provide clues to early detection of ESCC. Methods We conducted a population-based screening study in Linzhou, China, a region with high rates of ESCC. All subjects provided blood samples and underwent endoscopy with Lugol＇s iodine staining and biopsy. We selected a subset of 84 subjects stratified on worst squamous histological diagnosis and measured the serum concentrations of potential markers using commercially available ELISA tests for matrix metalloprotease-9, tissue inhibitor of matrix metalloprotease-1, copper/zinc superoxide dismutase, anti-p53 auto-antibodies, and soluble serum interleukin-2 receptor. Results Matrix metalloprotease-9 was significantly different by esophageal squamous dysplasia status with a median （interquartile range） for subjects without dysplasia of 150 （80-225）ng/ml and subjects with dysplasia/early cancer of 97（ 58 -155） ng/ml（P = 0. 033）, but the maximum sensitivity and specificity were low. The serum concentrations of the other markers tested showed no significant differences by category of worst histological diagnosis. Conclusion Serum matrix metalloprotease-9 concentrations could contribute to a primary screening test for an ESCC, but is insufficient alone.