Identification of Differentiation-Related Proteins in Gastric Adenocarcinoma Tissues by Proteomics

Xin Zhou; Kun Yao; Lang Zhang; Ying Zhang; Yin Han; Hui-Ling Liu; Xiang-Wen Liu; Gang Su; Wen-Zhen Yuan; Xiao-Dong Wei; Quan-Lin Guan; Bing-Dong Zhu

doi:10.1177/1533034615595792

Identification of Differentiation-Related Proteins in Gastric Adenocarcinoma Tissues by Proteomics

Technol Cancer Res Treat. 2016 Oct;15(5):697-706. doi: 10.1177/1533034615595792.

Authors

Xin Zhou¹, Kun Yao², Lang Zhang³, Ying Zhang⁴, Yin Han⁵, Hui-Ling Liu⁶, Xiang-Wen Liu⁴, Gang Su⁷, Wen-Zhen Yuan⁸, Xiao-Dong Wei⁶, Quan-Lin Guan⁹, Bing-Dong Zhu¹⁰

Affiliations

¹ Department of the First Clinical Medical College of Lanzhou University, Lanzhou, China Department of Oncology, the First Affiliated Hospital, Beilun Branch of Zhejiang University, Ningbo, Zhejiang, China Xin Zhou and Kun Yao contributed equally to this article.
² Department of the First Clinical Medical College of Lanzhou University, Lanzhou, China Department of Obstetrics and Gynecology, Gansu Provincial People's Hospital, Lanzhou, China Xin Zhou and Kun Yao contributed equally to this article.
³ Institute of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
⁴ Institute of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
⁵ Institute of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
⁶ Department of Obstetrics and Gynecology, Gansu Provincial People's Hospital, Lanzhou, China.
⁷ Department of Obstetrics and Gynecology, Gansu Provincial People's Hospital, Lanzhou, China Institute of Genetics, School of Basic Medical, Lanzhou University, Lanzhou, China.
⁸ Department of Surgical Oncology, the First Affiliated Hospital of Lanzhou University, Lanzhou, China.
⁹ Department of Surgical Oncology, the First Affiliated Hospital of Lanzhou University, Lanzhou, China guanquanlin@163.com.
¹⁰ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA Institute of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China bdzhu@lzu.edu.cn.

PMID: 27624754
DOI: 10.1177/1533034615595792

Abstract

There is a significant correlation between the degree of tumor differentiation and the survival of patients with gastric cancers. In this report, we compared proteomic differences between poorly differentiated gastric adenocarcinoma tissues and well-differentiated gastric adenocarcinoma tissues in order to identify differentiation-related proteins that may be closely correlated with differentiation of gastric cancer pathogenesis. We identified 7 proteins, of which calreticulin precursor, tapasinERP57 heterodimer, pyruvate kinase isozymes M1/M2 isoform M2, class Pi glutathione S-transferase, and chain A crystal structure of human enolase 1 were upregulated in poorly differentiated gastric adenocarcinoma compared with well-differentiated gastric adenocarcinoma, while myosin-11 isoform SM2A and actin alpha cardiac were downregulated. Two of them, pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 are enzymes involved in glycolytic pathway. The upregulation of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 in poorly differentiated gastric adenocarcinoma was confirmed by Western blotting and immunohistochemistry. Furthermore, we observed 107 cases with gastric adenocarcinoma and found that the high expression of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 correlates with tumor size (P = .0001 and P = .0017, respectively), depth of invasion (P = .0024 and P = .0261, respectively), and poor prognosis of patients. In conclusion, with this proteomic analysis, pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 were identified upregulated in poorly differentiated gastric adenocarcinoma comparing with well-differentiated gastric adenocarcinoma. The expression level of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 was significantly correlated with overall survival. Some of them would be differentiation-related cancer biomarkers and are associated with tumor metastasis, invasion, and prognosis.

Keywords: Image-Pro Plus; differentiation; gastric adenocarcinoma; glycolysis; immunohistochemistry; overall survival; proteomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / metabolism*
Adenocarcinoma / mortality
Adenocarcinoma / pathology*
Adult
Aged
Biomarkers, Tumor
Female
Humans
Immunohistochemistry
Male
Middle Aged
Neoplasm Grading
Neoplasm Staging
Prognosis
Proteome*
Proteomics*
Reproducibility of Results
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Stomach Neoplasms / metabolism*
Stomach Neoplasms / mortality
Stomach Neoplasms / pathology*
Tandem Mass Spectrometry

Substances

Biomarkers, Tumor
Proteome