Phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer

Han-Chen Huang; Xian-Zi Wen; Hua Xue; Run-Sheng Chen; Jia-Fu Ji; Lei Xu

doi:10.21147/j.issn.1000-9604.2019.05.07

Phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer

Chin J Cancer Res. 2019 Oct;31(5):771-784. doi: 10.21147/j.issn.1000-9604.2019.05.07.

Authors

Han-Chen Huang^{1

2}, Xian-Zi Wen³, Hua Xue^{1

2}, Run-Sheng Chen^{1

4}, Jia-Fu Ji³, Lei Xu^{5

6}

Affiliations

¹ Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing 100142, China.
⁴ Guangdong Geneway Decoding Bio-Tech Co.Ltd, Foshan 528316, China.
⁵ Centre for Cognitive Machines and Computational Health (CMaCH), School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
⁶ Department of Computer Science and Engineering, The Chinese University of Hong Kong, Hong Kong 999077, China.

PMID: 31814681
PMCID: PMC6856704
DOI: 10.21147/j.issn.1000-9604.2019.05.07

Abstract

Objective: Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer (GC) challenging. Here, we aimed to identify prognostic genes of GC using computational analysis.

Methods: We first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients' clinical information, we next identified prognostic genes using novel computational approaches. Phosphoglucose isomerase, also known as glucose-6-phosphate isomerase (GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state (E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition (EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets.

Results: We found that higher expression of GPI in GC correlated with prolonged survival of patients. Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage II/III. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells.

Conclusions: Our findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis, allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.

Keywords: Gastric cancer; gene expression profile; phosphoglucose isomerase; prognostic biomarker; tumor metabolism.