Identification of Differentiation-Related Proteins in Gastric Adenocarcinoma Tissues by Proteomics.
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.
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.
Xin
X
Zhou
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.
Kun
K
Yao
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.
Lang
L
Zhang
Institute of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
Ying
Y
Zhang
Institute of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
Yin
Y
Han
Department of Obstetrics and Gynecology, Gansu Provincial People's Hospital, Lanzhou, China.
Hui-Ling
HL
Liu
Institute of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
Xiang-Wen
XW
Liu
Department of Obstetrics and Gynecology, Gansu Provincial People's Hospital, Lanzhou, China Institute of Genetics, School of Basic Medical, Lanzhou University, Lanzhou, China.
Gang
G
Su
Department of Surgical Oncology, the First Affiliated Hospital of Lanzhou University, Lanzhou, China.
Wen-Zhen
WZ
Yuan
Department of Obstetrics and Gynecology, Gansu Provincial People's Hospital, Lanzhou, China.
Xiao-Dong
XD
Wei
Department of Surgical Oncology, the First Affiliated Hospital of Lanzhou University, Lanzhou, China guanquanlin@163.com.
Quan-Lin
QL
Guan
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.
Bing-Dong
BD
Zhu
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D020543:Proteome; D040901:Proteomics; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D053719:Tandem Mass Spectrometry
D014408:Biomarkers, Tumor; D020543:Proteome
Image-Pro Plus; differentiation; gastric adenocarcinoma; glycolysis; immunohistochemistry; overall survival; proteomics