微RNA-21和微RNA-146a在结直肠肿瘤中的表达及临床意义

Expressions and its clinical significance of microRNA-21 and microRNA-146a in colorectal neoplasms

目的探讨结直肠肿瘤患者组织和血清中miRNA-21和miRNA-146a的表达情况，并分析其临床意义。方法收集100例结直肠癌、80例结直肠腺瘤患者和65名健康对照者的内镜活检组织，同时收集其血清标本，应用实时荧光定量PCR检测miRNA-21和miRNA-146a的表达水平，分析其表达与临床病理特征间的关系，并评估血清差异表达的miRNA在结直肠肿瘤诊断中的价值。组间比较采用Mann-WhitneyU检验和Kruskal-Wallis检验；Spearman相关性检验用于分析组织和血清中miRNA表达的关联性。结果在结直肠癌和结直肠腺瘤患者病变组织中miRNA-21的表达分别为8．573±0．898和7．746±1．183，显著高于健康对照者的6．160±0．835（U=120．129、33．230，P均〈0．01）；在结直肠癌和结直肠腺瘤患者血清中的表达分别为1.829±0．303和1．624±0．226，也高于健康对照者的1．391±0．221（U=40．353、15．512，P均〈0．01）；miRNA-21在结直肠癌患者组织中和血清中的表达均高于结直肠腺瘤患者（U=11．384、10．189，P均〈O．01）。miRNA-21在结直肠癌患者中的高表达与肿瘤临床分期、淋巴结转移有关；miRNA-21在结直肠腺瘤中的表达水平与病理类型有关。Spearman分析结果示，miRNA-21在结直肠癌患者组织和血清中的表达呈正相关（r=0．459，P〈0．01）。miRNA-146a在结直肠癌患者组织中为2．556±0．351，血清中为0．249±0．038，低于健康对照者的3．428±0．328和0．279±0．053（U=102．134、30．111，P均〈0．01）；其在结直肠腺瘤患者组织中为3．255±0．332，血清中为0．290±0．036，与健康对照者比较差异无统计学意义（U=-3．936、3．180，P均〉0．05）。miRNA-146a在结直肠癌患者组织中和血清中的表达均低于结直肠腺瘤患者（U=73．809、21．123，P均〈0．01）。结直肠癌患者miRNA-146a的下降程度与肿瘤临床分期、肿瘤分化程度有关，而在结直肠腺瘤中的表达与ll缶床特征间无明显关系。根据ROC曲线分析，鉴别结直肠癌与健康者，血清miRNA-21、miRNA-146a及二者联合检测ROC的AUC分别为0．889、0．791和0．863；鉴别结直肠腺瘤与健康者，其AUC分别为0．784、0．692和0．761；鉴别结直肠癌与结直肠腺瘤患者，其AUC分别为0．705、0．820和0．713。结论血清miRNA-21和miRNA-146a的差异表达在结直肠癌的早期诊断中具有潜在的价值。

Objective To investigate the differences of miRNA-21 and miRNA-146a expression between colorectal neoplasms tissues and serum of the patients with colorectal neoplasm, and the clinical significance was analyzed. Methods The endoscopic biopsy tissues and serum samples of 100 colorectal cancer （CRC）, 80 colorectal adenoma （CRA） patients and 65 healthy controls were collected. The expressions of miRNA-21 and miRNA-146a were detected by quantitative real time polymerase chain reaction. The relationship between the expression and clinicopathological features were analyzed. And then, the diagnostic value of expression difference of serum miRNA in colorectal neoplasm were evaluated. The Mann-Whitney U test and Kruskal-Wallis test were performed for comparisons between groups, and the correlation of miRNA expression between tissues and serum was analyzed by Spearman test. ResultsThe expressions of miRNA-21 in the tissues of CRC and CRA were 8. 57± 0. 898 and 7. 746± 1. 183, respectively, which were significantly higher than that of healthy controls 6. 160±0. 835 （U= 120. 129 and 33. 230,both P〈0.01）. The expressions of miRNA-21 in the serum of CRC and CRA were 1. 829±0. 303 and 1. 624±0. 226, respeotively, which were higher than that of healthy controls 1. 391± 0. 221 （U=40. 353 and 15. 512, both P〈0. 01）. The expression of miRNA-21 in the serum and tissues of patients with CRC were both higher than those of patients with CRA （U=11. 384 and 10. 189, both P〈 0.01）. The expression of miRNA-21 in patients with CRC was associated with TNM stage and lymph node metastasis. The expression level of miRNA-21 in CRA was correlated with histological types. The results of Spearman analysis indicated that the expression of miRNA-21 in the tissues and serum of patients with CRC was positively correlated （r=0. 459 ,P〈0.01）. The expression of miRNA-146a in the tissues and serum of CRC patients were 2.556 ±0.351 and 0. 249 ±0. 038, respectively, which were lower than those of healthy controls （3. 428±0. 328 and 0.279±0.053） （U=102.134 and 30.111,both P〈 0.01）. The expression in the tissues and serum of CRA patients were 3. 255±0. 332 and 0. 290±0. 036, respectively, which were also lower than those of healthy controls, however the difference was not statistically significant （U= 3. 936 and 3. 180, both P〉0.05）. The expression of miRNA-146a in the tissues and serum of CRC patients were both lower than those of CRA patients （U= 73. 809 and 21. 123, both P〈0.01）. The degree of decreased expression of miRNA-146a in CRC patients was correlated with TNM staging and tumor differentiation degree, however there was no correlation between the expression in CRA and clinical features. According to receiver operating characteristic （ROC） curve analysis, the AUC of miRNA-21, miRNA-146a and a combination of them in CRC and health individuals was 0. 889, 0. 791 and 0. 863, respectively; in CRA and health individuals was 0. 784, 0. 692 and 0. 761, respectively; in CRC and CRA was 0. 705, 0. 820 and 0. 713, respectively. Conclusion The different expressions of miRNA-21 and miRNA-146a had potential values in early detection of colorectal cancer.