title: Autophagy-based survival prognosis in human colorectal carcinoma.
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.
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
authors.forename: Maopeng
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Bai
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
authors.forename: Sanqi
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
authors.forename: Fujing
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Basic Medicine, Harbin Medical University-Daqing, Heilongjiang, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D019540:Area Under Curve; D001343:Autophagy; D000071186:Beclin-1; D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D008928:Mitochondria / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; C491997:BECN1 protein, human; D000071186:Beclin-1; D014408:Biomarkers, Tumor; C502070:MAP1LC3B protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D051020:bcl-X Protein
keywords: Bcl-xL; Beclin 1; LC 3B; autophagy; colorectal carcinoma