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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2018.00650

Apolipoprotein E Overexpression Is Associated with The Tumor Progression and A Poor Survival in Colorectal Cancer

 Zhixun Zhao1, Shuangmei Zou2, Xu Guan3, Meng Wang1, Zheng Jiang3, Zheng Liu3, Chunxiang Li4,  Huixin Lin5, Xiuyun Liu2, Runkun Yang1, Yibo Gao4* and Xishan Wang1, 3*
  • 1Department of Colorectal Surgery, Second Affiliated Hospital of Harbin Medical University, China
  • 2Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, China
  • 3Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, China
  • 4National Cancer Center of China, China
  • 5Geneis (Beijing) Co. Ltd, China

Apolipoprotein E (ApoE) plays a key role in tumorigenesis and progression, such as cell proliferation, angiogenesis and metastasis. ApoE overexpression was associated with aggressive biological behaviors and poor prognosis in a variety of tumor according to previous studies. This study aimed to assess the prognostic value and explore the potential relationship with tumor progression in colorectal cancer (CRC). We collected the expression profiling microarray data from the Gene Expression Omnibus (GEO), investigated the ApoE expression pattern between the primary CRC and liver metastasis of CRC, and then explored the gene with prognostic significance based on the TCGA database. ApoE high expression was associated with poor overall survival (OS, p=0.015) and progression-free survival (PFS, p=0.004) based on the public databases. Next, ApoE expression was evaluated in two CRC cohorts by immunohistochemistry, of whom 306 cases were stage II and 201 cases were metastatic liver CRC. In the cohort of the liver metastasis, the ApoE expression was increasing in normal mucosa tissue, PCC and CLM in order. Meanwhile, the level of ApoE expression in stage II tumor sample which had no progression evidence in 5 years was lower than that in PCC of synchronous liver metastases. The high ApoE expression in PCC was an independent risk factor in both stage II (HR=2.023, [95% CI 1.297-3.154], p=0.002; HR=1.883, [95% CI 1.295-2.737], p=0.001; OS and PFS respectively) and simultaneous liver metastasis (HR=1.559, [95% CI 1.096-2.216], p=0.013; HR=1.541, [95% CI 1.129-2.104], p=0.006; OS and PFS respectively). However, the overexpression of ApoE could not predict the benefit from the chemotherapy in stage II. The study revealed that the relevance of the ApoE overexpression in CRC progression, conferring a poor prognosis in CRC patients especially for stage II and simultaneous liver metastasis. These finding may improve the prognostic stratification of patients for clinical strategy selection and promote CRC clinic outcomes.

Keywords: colorectal cancer, Apolipoprotein E (APOE), prognosis, Stage II, Simultaneous Liver Metastasis, biomarkers, chemotherapy

Received: 10 Oct 2018; Accepted: 30 Nov 2018.

Edited by:

Tao Huang, Shanghai Institutes for Biological Sciences (CAS), China

Reviewed by:

Hauke Busch, Universität zu Lübeck, Germany
Changlong Gu, Hunan University, China
Min Tang, University of Arizona, United States  

Copyright: © 2018 Zhao, Zou, Guan, Wang, Jiang, Liu, Li, Lin, Liu, Yang, Gao and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Yibo Gao, National Cancer Center of China, Beijing, China,
Dr. Xishan Wang, Department of Colorectal Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China,