Beclin 1和LC3作为转移性结直肠癌的预测生物标志物。

Beclin 1 and LC3 as predictive biomarkers for metastatic colorectal carcinoma.

作者信息

Zhao Hong, Yang Maopeng, Zhao Bin

机构信息

Harbin Medical University-Daqing, Heilongjiang, China.

Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China.

出版信息

Oncotarget. 2017 Aug 4;8(35):59058-59067. doi: 10.18632/oncotarget.19939. eCollection 2017 Aug 29.

Abstract

Autophagy is a highly conserved self-destructive process that disassembles dysfunctional or unnecessary cellular components. It plays an important role in cancer metastasis, which is of particular interest considering metastatic disease is the major cause of colorectal carcinoma (CRC) related mortality. Here, we investigated the immunohistochemical expression of autophagy-related protein Beclin 1 and Microtubule-associated protein 1A/1B-light chain 3 (LC3) within surgical CRC specimens, first in a training cohort (205 patients), then in an inner validation cohort (160 patients) and an independent cohort (161 patients). The expressions of Beclin 1 and LC3 were lower in metastatic CRC compared with non-metastatic CRC. Furthermore, we developed an autophagy-based classifier for metastatic prediction. This classifier, including Beclin 1, LC3 and carcinoembryonic antigen (CEA) level, resulted in 82.9% sensitivity and 89.8% specificity for metastatic detection in the training cohort. In the independent cohort, it achieved 77.9% sensitivity and 90.3% specificity in predicting the metastasis of CRC. These results suggested that low expression of Beclin 1 and LC3 contributed to a more aggressive cancer cell phenotype, and our autophagy-based classifier was a reliable tool for metastatic prediction in CRC.

摘要

自噬是一种高度保守的自我破坏过程,可分解功能失调或不必要的细胞成分。它在癌症转移中起重要作用,鉴于转移性疾病是结直肠癌(CRC)相关死亡的主要原因,这一点尤其值得关注。在此,我们首先在一个训练队列(205例患者)中,然后在一个内部验证队列(160例患者)和一个独立队列(161例患者)中,研究了结直肠癌手术标本中自噬相关蛋白Beclin 1和微管相关蛋白1A/1B轻链3(LC3)的免疫组化表达。与非转移性结直肠癌相比,转移性结直肠癌中Beclin 1和LC3的表达较低。此外,我们开发了一种基于自噬的转移预测分类器。该分类器包括Beclin 1、LC3和癌胚抗原(CEA)水平,在训练队列中对转移检测的灵敏度为82.9%,特异度为89.8%。在独立队列中,它在预测结直肠癌转移方面的灵敏度为77.9%,特异度为90.3%。这些结果表明,Beclin 1和LC3的低表达促成了更具侵袭性的癌细胞表型,并且我们基于自噬的分类器是结直肠癌转移预测的可靠工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b39/5601714/a80430100b76/oncotarget-08-59058-g001.jpg

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