结直肠癌细胞和组织Epac1表达临床意义

Expression characteristics of Epac1 in colorectal cancer and its clinical significance

目的环磷酸腺苷交换蛋白1(the exchange protein directly activated by cAMP1,Epac1)可活化Ras样GTP酶,且与许多肿瘤发生发展相关,但在结直肠癌中鲜见报道。本研究探讨Epac1在结直肠癌中的表达特征及其临床意义。方法蛋白质印迹法检测结肠癌细胞株(Caco2、HT29和SW480)及正常结肠上皮黏膜细胞株(FHC)中Epac1蛋白表达;免疫组化(EnVision法)检测西南医科大学附属医院2009-03-01-2012-03-01行结直肠癌手术治疗的79例癌组织配对79例正常组织标本,以及22例腺瘤组织标本中Epac1的表达,分析Epac1表达与结直肠癌患者临床病理特征及预后相关性。结果 Caco2、HT29、SW480和FHC细胞中Epac1蛋白相对表达量分别为0.756±0.050、0.862±0.076、1.042±0.078和0.593±0.057,Caco2、HT29和SW480中Epac1蛋白表达高于FHC,差异有统计学意义,P<0.05;结直肠癌组织、正常组织和腺瘤组织中Epac1表达率分别为65.8%(52/79)、11.4%(9/79)和22.7%(5/22),差异有统计学意义,χ~2=52.491,P<0.001;Epac1高表达与肿瘤TNM分期(χ~2=4.579,P=0.032)、浸润深度(χ~2=6.706,P=0.010)和淋巴结转移(χ~2=5.157,P=0.023)有关,而与肿瘤大小、肿瘤部位和分化程度无关,均P>0.05;Epac1高表达与低表达患者5年总生存率分别为53.8%和77.8%(χ~2=4.495,P=0.034),5年无病生存率分别为43.1%和53.9%(χ~2=4.956,P=0.026),差异均有统计学意义。结论 Epac1在结直肠癌细胞及组织中表达上调,其异常高表达可能参与结直肠癌的发生发展过程,Epac1对结直肠癌预后评价有一定参考价值。

OBJECTIVE Epacl,the exchange protein directly activated by cAMP1, can activate Ras-like GTPases and is associated with the development of many human tumors. However, the involvement of Epacl has not been estab- lished in colorectal cancer（CRC）. In this study,we investigated the expression characteristics of Epacl in CRC and its clin- ical significance. METHODS The expression levels of Epacl in colon cancer cell lines （Caco2, HT29,SW480） and normal human colon cells（FHC） were tested by Western Blotting. The expression levels of Epacl in 79 CRC tissues along with the cognate 79 paired adjacent normal tissues,and 22 cases of colorectal adenoma tissues that received surgical treatment from 2009-03-01 to 2012-03-01 in the Affiliated Hospital of Southwest Medical University were analyzed by immunohisto- chemistry（EnVision method）. The correlations between the expression of Epacl and the clinical pathological characteris-tics of CRC were also analyzed. The Kaplan-Meier method was used to explore the correlation between the Epacl expression and prognosis. RESULTS Western blot analysis showed that the expression levels of Epacl in colon cancer cell lines, Caco2 （0. 756±0. 050）, HT29 （0. 862±0. 076）, and SW480 （1. 042±0. 078） were significantly higher than that in human normal colon cell line, FHC （0. 593 ±0. 057） ,P〈0. 05. The expression levels of Epacl in CRC tissues, paired normal tis- sues,and adenoma tissues were 65.8%（52/79）,11.4%（9/79） and 22.7%（5/22） ,respectively （χ^2=52. 491,P〈0.01）. Overexpression of Epacl was closely associated with the TNM stage （χ^2=4. 579, P = 0. 032）, depth of invasion （χ^2= 6.706, P = 0.010）, and lymph node metastasis （χ^2=5. 157, P= 0. 023）, but was not correlated with tumor size, tumor lo- cation or degree of differentiation （P〈0.05）. The overall five-year survival rate of patients with high and low expression of Epacl was 53.8 % and 77.8% （χ^2= 4. 495, P= 0. 034） respectively, while the five-year disease-free survival rate was 43. 1% and 53.9%（χ^2=4. 956,P=0. 026）. CONCLUSIONS Epacl is up-regulated in colorectal cancer cells and tissues,and its abnormally high expression may be associated with the occurrence and development of CRC. Epacl can be used as a marker to predict the prognosis of patients with CRC.