Abstract
Gastric cancer (GC) has a high rate of morbidity and mortality among various cancers worldwide. The development of noninvasive diagnostic methods or technologies for tracking the occurrence of GC is urgent, and searching reliable biomarkers is considered.This study intended to directly discover differential biomarkers from GC tissues by two-dimension-differential gel electrophoresis (2D-DIGE), and further validate protein expression by western blotting (WB) and immunohistochemistry (IHC).Pairs of GC tissues (gastric cancer tissues and the adjacent normal tissues) obtained from surgery was investigated for 2D-DIEG.Five proteins wereconfirmed by WB and IHC, including glucose-regulated protein 78 (GRP78), glutathione s-transferase pi (GSTpi), apolipoprotein AI (ApoAI), alpha-1 antitrypsin (A1AT) and gastrokine-1 (GKN-1). Among the results, GRP78, GSTpi and A1ATwere significantlyup-regulated and down-regulated respectively in gastric cancer patients. Moreover, GRP78 and ApoAI were correlated with A1AT for protein expressions.This study presumes these proteins could be candidates of reliable biomarkers for gastric cancer.
Highlights
Theprevalence of gastric cancer is declining and varying geographically, it remains one of the most common cancers in Asian countries and is the fourth most commonly occurring cancer (9% of all cancers) worldwide
Biomarkers discovery based on 2D-DIGE Gastric cancer tissues were analyzed by 2D-DIGE and compared with paired normal tissues to search for the putative biomarkers of gastric cancer
It is important to have biomarkers for the diagnosis and followup of gastric cancer.carcinoembryonic antigen (CEA), carbohydrate antigen (CA19-9) and CA72-4 are not commonly used in clinical practices.The present study aimed to disclose putative biomarkers by comparing the differential proteins between matched cancer and normal tissues.Afterward, these putative biomarkers were examined in validation group.Five putative proteins, including glucose-regulated protein 78 (GRP78), glutathione s-transferase pi (GSTpi), apolipoprotein AI (ApoAI), alpha-1 antitrypsin (A1AT) and GKN-1, were identified by two-dimensiondifference gel electrophoresis (2D-DIGE), andmatrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) and fatherlyvalidated in 12 clinical patients.Among five putative proteins, GRP78 and GSTpi were significantly up-regulated and enhanced in cancer cells by western blotting and immunohistochemistry.In contrast,A1AT wassignificantlydown-regulated and had positive and negative correlation with the expression of ApoAI and GRP78
Summary
Theprevalence of gastric cancer is declining and varying geographically, it remains one of the most common cancers in Asian countries and is the fourth most commonly occurring cancer (9% of all cancers) worldwide. The agestandardized incidence rates (ASR) are greater than 20 per 100,000 in high risk countries such as China, Japan and Korea[1][2,3]. It is the second leading cause of cancer death in both sexes worldwide (737,000 deaths, 9.7% of the total).
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