Beclin 1 and LC3 as predictive biomarkers for metastatic colorectal carcinoma
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Hong Zhao1,2, Maopeng Yang2 and Bin Zhao3
1Harbin Medical University-Daqing, Heilongjiang, China
2Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China
3The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, China
Hong Zhao, email: email@example.com
Bin Zhao, email: firstname.lastname@example.org
Keywords: colorectal carcinoma, beclin 1, LC3, metastasis, biomarker
Received: July 11, 2017 Accepted: July 26, 2017 Published: August 04, 2017
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.
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