We recently showed that non-small cell lung carcinomas (NSCLCs) are of dismal prognosis when encompassing accelerated autophagic activity. The regulation of this abnormally functioning degradation system and its association with hypoxia and apoptosis in lung carcinoma patients is unexplored. In this study we used 115 NSCLC tissues to examine the immunohistochemical expression of four distinct molecules - the major regulator of autophagy Beclin 1, the anti-apoptotic and anti-autophagic protein Bcl-2, the pro-apoptotic and pro-autophagic protein BNIP3, and a marker of hypoxia and glucolysis, the glucose transporter Glut 1. Most cases showed reduced reactivity for Beclin 1 (62%) and Bcl-2 (82%) proteins, almost half of our sample revealed strong BNIP3 expression (57%), whereas most of the carcinomas strongly expressed Glut 1 antigen (71%). Beclin 1 expression showed no association with survival. Bcl-2 positivity was a marker of good prognosis (p = 0.04), whereas BNIP3 (p = 0.0004) and Glut 1 (p = 0.03) expression correlated with poor outcome in Stage I disease. Autophagic status was negatively associated with Bcl-2 (p = 0.0006), but positively with Glut 1 expression (p = 0.001). In conclusion, the accelerated autophagic status in NSCLC is unrelated to Beclin 1 and BNIP3 expression, but does show significant association with Bcl-2 reactivity. Furthermore, we showed important correlations between glucolysis and autophagy, guiding new pathways in future lung carcinoma research.

译文

:我们最近发现,非小细胞肺癌(NSCLC)包含加速自噬活性时预后不良。肺癌患者中这种功能异常的降解系统的调节及其与缺氧和细胞凋亡的关系尚待探索。在这项研究中,我们使用了115个非小细胞肺癌组织来检查四种不同分子的免疫组织化学表达-自噬Beclin 1的主要调节剂,抗凋亡和抗自噬蛋白Bcl-2,促凋亡和自噬蛋白BNIP3,葡萄糖转运蛋白Glut 1是缺氧和糖酵解的标志。大多数病例显示Beclin 1(62%)和Bcl-2(82%)蛋白的反应性降低,几乎一半的样本显示BNIP3表达强(57%),而大多数癌症强烈表达Glut 1抗原(71%)。 Beclin 1的表达与存活率无关。 Bcl-2阳性是预后良好的标志(p = 0.04),而BNIP3(p = 0.0004)和Glut 1(p = 0.03)的表达与I期疾病的不良预后相关。自噬状态与Bcl-2呈负相关(p = 0.0006),但与Glut 1表达呈正相关(p = 0.001)。总之,NSCLC中自噬状态的加速与Beclin 1和BNIP3的表达无关,但确实与Bcl-2的反应性显着相关。此外,我们显示了糖酵解与自噬之间的重要关联,为未来肺癌研究的新途径提供了指导。

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