1. iTRAQ-Based Quantitative Proteomics Approach Identifies Novel Diagnostic Biomarkers That Were Essential for Glutamine Metabolism and Redox Homeostasis for Gastric Cancer
- Author
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Li Gan, Chenghua Zhang, Yujiang Chen, Zhen Jiang, Qin Yu, Xingli Ji, Zhi Wang, Rui Zhu, Yuewang Jia, Li Wang, Linfeng Wang, Juexi Li, Yu Xiong, and Hao Luo
- Subjects
0301 basic medicine ,Male ,Proteomics ,medicine.medical_specialty ,Glutamine ,Clinical Biochemistry ,Quantitative proteomics ,Gastroenterology ,Mass Spectrometry ,03 medical and health sciences ,Glutaminase ,Stomach Neoplasms ,Internal medicine ,medicine ,Biomarkers, Tumor ,Diagnostic biomarker ,Humans ,Clinical significance ,Stage (cooking) ,030102 biochemistry & molecular biology ,Receiver operating characteristic ,business.industry ,Cancer ,Gene Expression Regulation, Developmental ,medicine.disease ,Early Gastric Cancer ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Female ,business ,gamma-Glutamylcyclotransferase ,Isobaric tag for relative and absolute quantitation ,Chromatography, Liquid - Abstract
Purpose To screen the novel biomarkers for gastric cancer and to determine the values of glutaminase 1 (GLS1) and gamma-glutamylcyclotransferase (GGCT) for detecting gastric cancer. Experimental design A discovery group of four paired gastric cancer tissue samples are labeled with Isobaric tag for relative and absolute quantitation agents and identified with LC-ESI-MS/MS. A validation group of 168 gastric cancer samples and 30 healthy controls are used to validate the expression of GLS1 and GGCT. Results Four hundred and thirty-one proteins are found differentially expressed in gastric cancer tissues. Of these proteins, GLS1 and GGCT are found overexpressed in gastric cancer patients, with sensitivity of 75.6% (95% CI: 69-82.2%) and specificity of 81% (95% CI: 75-87%) for GLS1, and with sensitivity of 63.1% (95% CI: 55.7-71.5%) and specificity of 60.7% (95% CI: 53.3-68.2%) for GGCT. The co-expression of GLS1 and GGCT in gastric cancer tissues has sensitivity of 78.1% (95% CI: 70.1-86.1%) and specificity of 86.5% (95% CI: 79.5-93.4%). Moreover, both GLS1 and GGCT present higher expression of 82.6% (95% CI: 68.5-99.4%) and 73.9% (95% CI: 54.5-93.3%) in lymph node metastasis specimen than those in non-lymph node metastasis specimen. The areas under ROC curves are up to 0.734 for the co-expression of GLS1 and GGCT in gastric cancer. The co-expression of GLS1 and GGCT is strongly associated with histological grade, lymph node metastasis, and TNM stage Ⅲ/Ⅳ. Conclusions and clinical relevance The present study provides the quantitative proteomic analysis of gastric cancer tissues to identify prognostic biomarkers of gastric cancer. The co-expression level of GLS1 and GGCT is of great clinical value to serve as diagnostic and therapeutic biomarkers for early gastric cancer.
- Published
- 2018