目的探讨Runt相关转录因子3(Runx3)和染色质解旋酶DNA结合蛋白5(CHD5)基因在结直肠癌组织中的表达及临床意义。方法采用实时荧光定量聚合酶链反应(qRT-PCR)和Western blotting方法检测96例新鲜结直肠癌组织、对应的癌旁10Cm正常组织以及72例腺瘤中的Runx3和CHD5基因的表达,分析其与结直肠癌临床病理特征的关系以及诊断价值和预后关系。结果Runx3和CHD5mRNA、蛋白在结直肠癌组织中的相对表达量为0.35±0.00、0.28±0.02和0.26±0.02、0.31±0.01,显著低于癌旁正常组织中的相对表达量0.954-0.02、0.92±0.02和0.89±0.03、0.93±0.02(t=2.36.P〈0.05:t=1.25,P〈0.05;t=1.37,P〈0.05;t=1.13,P〈0.05)以及腺瘤中的相对表达量0.89±0.02、0.90±0.02和0.85±0.02、0.87±0.04(t=2.27,P〈0.05;t=2.16,P〈0.05;t=1.25,P〈0.05;t=2.65,P〈0.05)。Runx3和CHD5的表达与结直肠癌TNM分期(X2=4.65,P=0.031;X2=7.89,P=0.005)、浸润深度(X2=4.17,P=0.041;X2=4.86,P=0.028)、淋巴结转移(X2=4.20,P=0.040;X2=7.02,P=0.008)以及分化程度(X2=7.31,P=0.036;X2=9.54,P=0.023)呈负相关。线性相关性分析显示两基因表达呈正相关(r=0.572,P=0.001)。受试者特征(ROC)曲线进行评价表明Runx3、CHD5在结直肠癌中具有诊断价值(曲线下面积分别为0.712、0.745,敏感性和特异性分别是45.9%、52.5%和83.6%、81.4%)。Runx3和CHD5均低表达组与其他患者组在总生存时间(X2=8.156,P〈0.05)及无进展生存时间(X2=6.325,P〈0.05)上的差异具有统计学意义。结论Runx3和CHD5在结直肠癌中低表达,两基因共同检测可以作为结直肠癌诊断靶标以及预后指标。
Objective To investigate the expressions and clinical significances of Runt-domain-related 3 (Runx3) and chromodomain helicase DNA-binding protein 5 (CHD5) in colorectal cancer. Methods Ninety-six colorectal cancer tissue samples and matched adjacent normal tissues and 72 colorectal adenoma tissues were collected. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the mRNA and protein expression of Runx3 and CHD5. The associations of Runx3 and CHD5 expression with clinical pathological characteristics, diagnostic value and prognosis relationship of patients were further analyzed. Results Runx3 and CHD5 relative expressions of mRNA and protein were 0.35 ± 0.00, 0.28 ± 0.02 and 0.26 ± 0.02, 0.31 ± 0.01, which were significantly lower than those in the matched adjacent tissues0.95±0.02, 0.92±0.02and0.89±0.03, 0.93±0.02 (t=2.36, P〈0.05; t=1.25, P〈0.05; t=1.37, P〈0.05; t =1.13, P〈0.05) and colorectal adenoma tissues 0.89±0.02, 0.90±0.02 and 0.85±0.02, 0.87±0.04 (t=2.27, P〈0.05; t=2.16, P〈0.05; t=1.25, P〈0.05; t=2.65, P〈 0.05 ). Runx3 and CHD5 expressions differed significantly between tumors with different TNM stages (X2 = 4.65, P = 0. 031 ; X2 = 7.89, P = 0. 005 ), depths of tumor invasion (X2 = 4.17, P = 0. 041 ; X2 = 4.86, P =0.028), lymph node statuses (X2 = 4.20, P = 0. 040 ; X2 = 7.02, P = 0. 008 ), or histological differentiation (X2 = 7.31, P = 0.036 ; X2 = 9.54, P = 0.023 ). Linear correlation analysis showed that the expressions of the two genes were positively correlated (r = 0. 572, P = 0. 001 ). Receiver operating characteristic (ROC) curve showed that Runx3 and CHD5 had diagnostic value (AUC were 0.712, 0.745 ; sensitivity and specificity were 45.9%, 52.5% and 83.6%, 81.4% respectively). Runx3 and CHD5 both low expression group compared with the other patient groups in Overall survival time (X2 = 8. 156, P 〈 0.05 ) and progression-free survival (X2 =6. 325, P 〈 0.05 ) h