Li Bao-Zhong, Chen Zhao-Li, Shi Su-Sheng, Feng Xiao-Li, Tan Xiao-Gang, Zhou Fang, He Jie
Departments of Thoracic Surgery, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Chin J Cancer. 2013 Jul;32(7):403-9. doi: 10.5732/cjc.012.10233. Epub 2013 Mar 8.
Biomarker identification is crucial for the selection of patients who might benefit from radiotherapy. To explore potential markers for response and prognosis in patients with locally advanced esophageal carcinoma treated with radiotherapy followed by surgery, we evaluated the expression of cell cycle checkpoint-related proteins Chk2, Cdc25C, and Cyclin D1. A total of 56 patients with locally advanced esophageal squamous cell carcinoma were treated with radiotherapy followed by surgery. Pretreatment tumor biopsy specimens were analyzed for Chk2, Cdc25C, and Cyclin D1 expression by immunohistochemistry. High expression of Chk2, Cyclin D1, and Cdc25C was observed in 44 (78.6%), 15 (26.8%), and 27 (48.2%) patients, respectively. The median survival was 16 months (range, 3-154 months), with a 5-year overall survival rate of 19.6%. Overexpression of Chk2 was associated with smoking (P = 0.021), overexpression of Cdc25C was associated with patient age (P = 0.033) and tumor length (P = 0.001), and overexpression of Cdc25C was associated with pathologic complete response (P = 0.038). Univariate analysis demonstrated that overexpression of Cdc25C and pathologic complete response was associated with better survival. In multivariate analysis, Cdc25C was the most significant independent predictor of better survival (P = 0.014) for patients treated with radiotherapy followed by surgery. Overexpression of Cdc25C was significantly associated with pathologic complete response and better survival of patients with locally advanced esophageal cancer treated with radiotherapy followed by surgery. These results suggest that Cdc25C may be a biomarker of treatment response and good prognosis for esophageal carcinoma patients. Thus, immunohistochemical staining of Cdc25C in a pretreatment specimen may be a useful method of identifying optimal treatment for patients with esophageal carcinoma.
生物标志物的鉴定对于选择可能从放疗中获益的患者至关重要。为了探索接受放疗后手术的局部晚期食管癌患者的反应和预后潜在标志物，我们评估了细胞周期检查点相关蛋白Chk2、Cdc25C和细胞周期蛋白D1的表达。共有56例局部晚期食管鳞状细胞癌患者接受了放疗后手术。通过免疫组织化学分析预处理肿瘤活检标本中Chk2、Cdc25C和细胞周期蛋白D1的表达。分别在44例（78.6%）、15例（26.8%）和27例（48.2%）患者中观察到Chk2、细胞周期蛋白D1和Cdc25C的高表达。中位生存期为16个月（范围3 - 154个月），5年总生存率为19.6%。Chk2的过表达与吸烟相关（P = 0.021），Cdc25C的过表达与患者年龄（P = 0.033）和肿瘤长度（P = 0.001）相关，Cdc25C的过表达与病理完全缓解相关（P = 0.038）。单因素分析表明，Cdc25C的过表达和病理完全缓解与更好的生存率相关。在多因素分析中，Cdc25C是接受放疗后手术患者更好生存率的最显著独立预测因子（P = 0.014）。Cdc25C的过表达与病理完全缓解以及接受放疗后手术的局部晚期食管癌患者的更好生存率显著相关。这些结果表明，Cdc25C可能是食管癌患者治疗反应和良好预后的生物标志物。因此，预处理标本中Cdc25C的免疫组织化学染色可能是识别食管癌患者最佳治疗方法的有用手段。
