目的： 观察生长阻滞和DNA损伤诱导基因（growth arrest and DNA-damage-inducible 45, Gadd45 ）家族在食管鳞状细胞癌（esophageal squamous cell carcinoma, ESCC）中的表达，并探讨其临床意义。 方法: 选取河北医科大学第四医院2004-2008年间食管鳞癌患者128例的癌组织和癌旁组织标本。RT-PCR检测 Gadd45家族Gadd45A、Gadd45B和Gadd45G mRNA在食管鳞癌组织及癌旁组织中的表达，免疫组织化学方法检测Gadd45A、Gadd45B和Gadd45G蛋白在食管鳞癌组织及癌旁正常组织中的表达情况，分析 Gadd45A、Gadd45B和Gadd45G 表达与食管鳞状细胞癌的临床病理特征和预后之间的关系。 结果: 与癌旁组织相比，食管鳞癌组织中 Gadd45A mRNA表达水平显著升高\[(0.8924±0.3457) vs (0.6123±0.2132)，P<0.05\]； Gadd45B mRNA表达水平没有显著变化\[(0.8256±0.3110) vs (0.8173±0.3069)，P>0.05\]； Gadd45G mRNA表达水平显著降低\[(0.3855±0.1210) vs (0.8214±0.3069)，P<0.05\]，癌组织中 Gadd45G mRNA表达与TNM 分期和组织学分化程度密切相关。Gadd45A在癌旁组织中的蛋白表达以细胞核着色为主，而在部分肿瘤组织中表现为细胞质表达模式。与癌旁组织相比，食管鳞癌组织中Gadd45A的表达显著升高（χ2=55.603，P=0.000）；Gadd45B的表达没有显著性差异（χ2=0.456，P=0500）；Gadd45G的表达显著降低（χ2= 70.134，P=0.000）。Ⅲ期和Ⅳ期食管鳞癌患者Gadd45G蛋白表达水平显著低于Ⅰ期和Ⅱ期患者（χ2=5.768，P=0.016），低分化组的Gadd45G蛋白阳性表达率显著低于中高分化组（χ2=4.483，P=0.034）。Gadd45G阳性患者的5年存活率明显高于阴性患者（44% vs 21%，P<0.05）；Cox模型分析显示，Gadd45G蛋白的表达是食管鳞癌患者的一个独立预后因素。 结论: Gadd45A和Gadd45G 基因在食管鳞癌中的异常表达可能参与了食管鳞癌的发生、发展。

Objective : To investigate the expression of growth arrest and DNA-damage-inducible 45 (Gadd45) gene family members in esophageal squamous cell carcinoma (ESCC) and discuss its clinical significance. Methods: ESCC tissues and paracancerous tissues of one hundred and twenty-eight patients with ESCC from the Fourth Hospital Affiliated to Hebei Medical University during 2004-2008 were included in this study. The expressions of Gadd45A, Gadd45B and  Gadd45G mRNA in the ESCC tissues and paracancerous tissues were detected by RT-PCR. The protein expressions of Gadd45A, Gadd45B and Gadd45G in ESCC tissues and paracancerous tissues were detected by using immunohistochemistry methods. The relation was analyzed between the expressions of Gadd45A, Gadd45B and  Gadd45G and the clinical pathologic characteristics and prognosis of ESCC. Results: Compared to the paracancerous tissues, the expression of Gadd45A mRNA in the tumor tissues was significantly increased (\[0.8924±0.3457\] vs \[0.6123±0.2132\], P<005\],  Gadd45B mRNA showed no significantly changes (\[0.8256±0.3110\] vs \[0.8173±0.3069), P>0.05\], Gadd45G mRNA was significantly decreased (\[0.3855±0.1210\] vs \[0.8214±0.3069\], P<0.05, and the expression of Gadd45G mRNA was closely associated with TNM stage and histological differentiation. The expression of Gadd45A in the paracancerous tissues was mainly stained in nucleolus, while part of the tumor tissues demonstrated a cytoplasm expression mode. Compared with the paracancerous tissues, the expression of Gadd45A in the tumor tissues was significantly increased (χ2=55.603, P=0.000), Gadd45B showed no significant difference (χ2=0.456, P=0.500), and Gadd45G was significantly decreased (χ2= 70.134, P=0.000). The expression of Gadd45G in patients in phase Ⅲ and Ⅳwas significantly lower than that in patients in phaseⅠ and Ⅱ (χ2=5.768, P=0.016), and was significantly lower in the low differentiation group than in the high and moderate differentiation groups (χ2=4.483, P=0.034). The 5-year survival rate of patients with Gadd45G-positive was significantly higher than that of patients with Gadd45G-negative (44% vs 21%, P<0.05); Cox model analysis shows that Gadd45G expression was an independent prognostic factor for ESCC. Conclusion: Aberrant expression of Gadd45A and Gadd45G may participate in the development and progression of ESCC.

国家自然科学基金资助项目（No. 81101854）