Autophagy-based survival prognosis in human colorectal carcinoma

Abstract

// Maopeng Yang 1, * , Hong Zhao 1, * , Li Guo 1 , Qingyuan Zhang 1 , Ling Zhao 1 , Shuping Bai 1 , Minghui Zhang 1 , Sanqi Xu 1 , Fujing Wang 2 , Xiaohong Wang 1 , Bin Zhao 3 1 Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China 2 Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Heilongjiang, China 3 College of Basic Medicine, Harbin Medical University-Daqing, Heilongjiang, China * These authors have contributed equally to this work Correspondence to: Fujing Wang, e-mail: fujingwang@yeah.net Xiaohong Wang, e-mail: drxiaohongwang@163.com Bin Zhao, e-mail: bin.science@gmail.com Keywords: Colorectal carcinoma, autophagy, Beclin 1, LC 3B, Bcl-xL Received: January 05, 2015      Accepted: January 07, 2015      Published: January 20, 2015 ABSTRACT 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.