Autophagy-based survival prognosis in human colorectal carcinoma
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Maopeng Yang1,*, Hong Zhao1,*, Li Guo1, Qingyuan Zhang1, Ling Zhao1, Shuping Bai1, Minghui Zhang1, Sanqi Xu1, Fujing Wang2, Xiaohong Wang1, Bin Zhao3
1Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China
2Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Heilongjiang, China
3College of Basic Medicine, Harbin Medical University-Daqing, Heilongjiang, China
*These authors have contributed equally to this work
Fujing Wang, e-mail: [email protected]
Xiaohong Wang, e-mail: [email protected]
Bin Zhao, e-mail: [email protected]
Keywords: Colorectal carcinoma, autophagy, Beclin 1, LC 3B, Bcl-xL
Received: January 05, 2015 Accepted: January 07, 2015 Published: January 20, 2015
The role of autophagy in cancers is controversial. Here we aim to determine the prognostic significance of autophagy in colorectal carcinoma patients, thereby allowing more rational development of therapeutic strategies. Through transmission electron microscopy, our data first demonstrated high frequency of defective mitochondria was strongly associated with poor overall survival in colorectal carcinoma. Next immunohistochemical study showed the expressions of Beclin 1, LC3B and Bcl-xL in both the center of tumor and adjacent noncancerous mucosal region were also correlated with overall survivals. We developed an autophagy signature for prognosis based on these three major autophagic proteins, further analysis suggested it was an independent prognostic biomarker and had its value even within single clinical stage. Combined TNM stage and this signature could significantly improve the accuracy of survival prognosis. To validate these immunohistochemical results, an internal testing cohort and an independent population were also included. Our findings suggest that autophagy plays an important role in the clinical cancer progression. Therefore autophagic proteins may be valuable prognostic biomarkers in the therapy of colorectal carcinoma and possibly other types of cancers.
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