Wu Shuhua, Sun Chenbo, Tian Dong, Li Yangyang, Gao Xiangqian, He Shuang, Li Tangyue
Department of Pathology, Binzhou Medical University Hospital Binzhou, Shandong Province, China.
Department of Pathology, Binzhou Medical University Binzhou, Shandong Province, China.
Int J Clin Exp Pathol. 2015 Apr 1;8(4):3882-91. eCollection 2015.
Autophagy is related to cancer and other diseases, and compromised autophagy could promote chromosome instability associated with carcinogenesis and tumor progression. The role of autophagy in the growth and metastasis of colorectal cancer (CRC) remains poorly understood. Beclin1 mediates autophagic initiation, and LC3 is a specific marker for autophagy. Inactivation of mTOR caused by cellular hypoxia or energy deficiency induces autophagic activity. This study aims to examine the expression and clinical significance of these proteins in CRC. Immunohistochemistry results showed that the positive expression rates of Beclin1, LC3, and mTOR in cancer tissues were 90.50%, 87.19%, and 46.28%, respectively, which were higher than those in adjacent tissues (P < 0.05). Differentiation degree and lymph node metastasis were associated with LC3 overexpression (P < 0.05) but not with Beclin1 (P > 0.05). Lymph node metastasis was also related to mTOR. Spearman analysis results showed that LC3 expression was positively correlated with Beclin1 but negatively correlated with mTOR (r = 0.593 and -0.165, respectively; P < 0.01). Beclin1 expression was also not associated with mTOR (P > 0.05). Survival analysis further indicated that LC3, mTOR, and lymph node metastasis were independent prognostic factors in CRC. Real-time PCR results and Western blot indicated that Beclin1, LC3, and mTOR expression in CRC was significantly higher than that in adjacent tissues (P < 0.01). The aberrant protein expression may be associated with the development and progression of CRC. The LC3 and mTOR genes must be simultaneously detected to evaluate progression and prognosis of CRC.
自噬与癌症及其他疾病相关，自噬功能受损会促进与致癌作用和肿瘤进展相关的染色体不稳定。自噬在结直肠癌（CRC）生长和转移中的作用仍知之甚少。Beclin1介导自噬起始，而LC3是自噬的特异性标志物。细胞缺氧或能量缺乏导致的mTOR失活会诱导自噬活性。本研究旨在检测这些蛋白在结直肠癌中的表达及临床意义。免疫组织化学结果显示，Beclin1、LC3和mTOR在癌组织中的阳性表达率分别为90.50%、87.19%和46.28%，高于癌旁组织（P<0.05）。分化程度和淋巴结转移与LC3过表达相关（P<0.05），但与Beclin1无关（P>0.05）。淋巴结转移也与mTOR有关。Spearman分析结果显示，LC3表达与Beclin1呈正相关，但与mTOR呈负相关（r分别为0.593和 -0.165；P<0.01）。Beclin1表达也与mTOR无关（P>0.05）。生存分析进一步表明，LC3、mTOR和淋巴结转移是结直肠癌的独立预后因素。实时PCR结果和Western印迹表明，结直肠癌中Beclin1、LC3和mTOR的表达显著高于癌旁组织（P<0.01）。异常的蛋白表达可能与结直肠癌的发生和进展有关。必须同时检测LC3和mTOR基因以评估结直肠癌的进展和预后。
