自噬相关基因Beclin1、LC3与大肠癌多药耐药性的相关性

Expression of autophagy-related genes Beclin1,LC3 and their relationships with multidrug resistance in colorectal carcinoma

目的检测自噬相关基因Beclin1、LC3和多药耐药基因LRP、GST-π、TopoⅡ在大肠癌中的表达,探讨自噬对大肠癌多药耐药性(multidrug resistance,MDR)的影响。方法应用免疫组化EnVision法检测202例大肠癌中Beclin1、LC3、LRP、GST-π和TopoⅡ的表达,并结合临床病理参数进行分析。结果 Beclin1和LC3蛋白在大肠癌中的阳性率(90.10%、86.63%)均明显高于正常大肠黏膜(48.0%、40.0%),差异具有统计学意义(P<0.05),且LC3蛋白在中+低分化大肠癌中的表达(92.52%、90.00%)高于高分化大肠癌(72.73%),在淋巴结转移组的表达(94.31%)高于无淋巴结转移组(80.70%),差异具有统计学意义(P<0.05)。LRP、GST-π和TopoⅡ在大肠癌中的阳性率分别为94.55%、71.78%和97.03%,且TopoⅡ在大肠癌男性患者中的表达(100%)略高于女性患者(93.88%),差异具有统计学意义(P<0.05)。经Spearman相关性分析,在大肠癌中,Beclin1蛋白表达与LC3、LRP及GST-π蛋白表达均呈正相关,相关系数分别为0.552、0.140和0.160(P<0.05);LC3蛋白表达与LRP、GST-π蛋白表达均呈正相关,相关系数分别为0.162和0.142(P<0.05)。Kaplan-Meier生存分析显示,Beclin1阳性、LC3阳性、GST-π阴性、无淋巴结转移者5年生存率高于Beclin1阴性、LC3阴性、GST-π阳性及淋巴结转移者,多因素分析显示,LC3、GST-π和淋巴结转移是影响大肠癌患者术后生存的独立因素。结论 Beclin1、LC3在大肠癌组织中表达增加,可能与大肠癌的发生、发展及MDR有关;检测Beclin1、LC3蛋白表达对判断大肠癌的预后以及合理筛选有效的化疗药物具有重要参考价值。

Purpose To investigate the expression of autophagy-related genes Beelinl, LC3 and the impact of them on muhidrug re- sistance in colorectal carcinoma （CRC）. Methods Immunohistochemistry was employed to detect the expression of Beclinl, LC3, LRP, GST-π and Topo Ⅱ in 202 specimens of CRC. Results The positive expression of Beclinl and LC3 in CRC was 90. 10% and 86. 63% , and the positive rate of them in normal colorectal mucosa was 48. 0% and 40. 0% , respectively, the differences were statisti- cally significant （P 〈 0. 05）. Moreover, the expression of LC3 in moderately and poorly differentiated CRC was higher than that in well differentiated CRC, and the positive rate of LC3 in CRC with lymph node metastasis was higher than that in CRC without lymph node metastasis. Overexpression of LRP, GST-π and Topo Ⅱ was found in 94. 55%, 71.78% and 97.03% of CRC, respectively. The ex- pression of Beclinl was found to have a positive correlation with LC3, LRP and GST-π, the correlation coefficient was 0. 552, 0. 140 and 0. 160, respectively （P 〈 0. 05） , while LC3 was positively associated with LRP and GST-π, the correlation coefficient was 0. 162 and 0. 142 （P 〈 0. 05）. Kaplan-Meier analysis reveled that the five-year survival rate of patients without lymphnode metastasis, posi- tive expression of Beclinl, LC3 and negative expression of GST-π was higher than those with lymphnode metastasis, negative expres- sion of Beclinl, LC3, and positive expression of GST-π. Conclusions The expression of both Beclinl and LC3 is increased and may be related to the development and progress of colorectal carcinoma and MDR. The combined detection of Beclinl and LC3 is important for patients with colorectal carcinoma in prognosis and optimal therapy.