[NF-E1b在结直肠癌组织中的表达及其临床意义]

Xu Kai, Chen Lei, Di Jiabo, Wang Zaozao, Wang Aidong, Wu Wei, Wu Fan, Jiang Beihai, Su Xiangqian

Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education), Department of Gastrointestinal Surgery IIII(, Peking University Cancer Hospital and Institute, Beijing 100142, China.

Zhonghua Wei Chang Wai Ke Za Zhi. 2016 Jun;19(6):685-9.

OBJECTIVE

To explore the expression of NF-E1b in colorectal cancer tissues and its association with various clinicopathological parameters and prognosis of the patients.

METHODS

Clinicopathological and follow-up data of 168 colorectal cancer patients undergoing radical operation at Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute from 2005 to 2012 were retrospectively analyzed, including 96 males and 72 females, with mean age of (57.8±11.2) years. The expression of NF-E1b protein was detected in samples of 168 resected colorectal cancer tissues and 45 adjacent non-cancerous tissues by immunohistochemistry. The expression rates of NF-E1b were compared among different clinicopathological features. Moreover, the association between NF-E1b expression and prognosis was analyzed.

RESULTS

The expression of NF-E1b protein located mainly in cytoplasm. Positive rate of NF-E1b expression in adjacent non-cancerous tissues was 17.8% (8/45), which was obviously lower than 67.9%(114/168) of cancer tissues with significant difference (χ(2)=36.376, P=0.000). Clinicopathological parameters analysis suggested that the expression level of NF-E1b in cancer tissues was associated with age (χ(2)=4.862, P=0.030), TNM staging (χ(2)=10.969, P=0.002), lymph node metastasis (χ(2)=7.390, P=0.008) and distal metastasis (χ(2)=17.887, P=0.000). The median follow-up time was 23(1-77) months. The overall 5-year survival of this cohort was 33.3%. Colorectal cancer patients with high levels of NF-E1b expression showed a worse overall survival compared with those with low levels of NF-E1b expression (18.4% vs. 56.6%, P=0.000). Univariate Cox regression analysis showed that tumor location (P=0.034), tumor size (P=0.003), TNM staging (P=0.000), depth of tumor invasion (P=0.009), lymph node metastasis (P=0.000), distant metastasis (P=0.000) and NF-E1b expression level (P=0.001) were associated with the prognosis of colorectal cancer patients. Multivariate Cox regression analysis revealed that tumor diameter >4 cm (HR=2.193,95% CI:1.334 to 3.603, P=0.002), distant metastasis (HR=2.064, 95% CI:1.160 to 3.672, P=0.014) and high NF-E1b expression (HR=1.994,95% CI:1.068 to 3.724, P=0.030) were independent risk factors of predicting poor prognosis of colorectal cancer patients.

CONCLUSIONS

NF-E1b expression up-regulates in colorectal cancer tissues. High expression of NF-E1b is associated with poor prognosis of colorectal cancer patients. NF-E1b may serve as a potential target of the treatment for colorectal cancer.

目的

探讨NF-E1b在结直肠癌组织中的表达及其与患者临床病理参数和预后的关系。

方法

回顾性分析2005年至2012年在北京大学肿瘤医院暨研究所胃肠外科接受根治性手术的168例结直肠癌患者的临床病理及随访资料，其中男性96例，女性72例，平均年龄（57.8±11.2）岁。采用免疫组织化学法检测168例切除的结直肠癌组织及45例癌旁非癌组织样本中NF-E1b蛋白的表达。比较不同临床病理特征下NF-E1b的表达率。此外，分析NF-E1b表达与预后的关系。

结果

NF-E1b蛋白表达主要位于细胞质。癌旁非癌组织中NF-E1b表达阳性率为17.8%（8/45），明显低于癌组织的67.9%（114/168），差异有统计学意义（χ(2)=36.376，P=0.000）。临床病理参数分析表明，癌组织中NF-E1b的表达水平与年龄（χ(2)=4.862，P=0.030）、TNM分期（χ(2)=10.969，P=0.002）、淋巴结转移（χ(2)=7.390，P=0.008）及远处转移（χ(2)=17.887，P=0.000）有关。中位随访时间为23（1 - 77）个月。该队列的5年总生存率为33.3%。NF-E1b表达水平高的结直肠癌患者总体生存率低于NF-E1b表达水平低的患者（18.4%对56.6%，P=0.000）。单因素Cox回归分析显示，肿瘤部位（P=0.034）、肿瘤大小（P=0.003）、TNM分期（P=0.000）、肿瘤浸润深度（P=0.009）、淋巴结转移（P=0.000）、远处转移（P=0.000）及NF-E1b表达水平（P=0.001）与结直肠癌患者的预后相关。多因素Cox回归分析显示，肿瘤直径>4 cm（HR=2.193，95%CI：1.334至3.603，P=0.002）、远处转移（HR=2.064，95%CI：1.160至3.672，P=0.014）及NF-E1b高表达（HR=1.994，95%CI：1.068至3.724，P=0.030）是预测结直肠癌患者预后不良的独立危险因素。