Abstract
Gastric cancer (GC) has significant morbidity and mortality worldwide and especially in China. Its molecular pathogenesis has not been thoroughly elaborated. The acknowledged biomarkers for diagnosis, prognosis, recurrence monitoring and treatment are lacking. Proteins from matched pairs of human GC and adjacent tissues were analyzed by a coupled label-free Mass Spectrometry (MS) approach, followed by functional annotation with software analysis. Nano-LC-MS/MS, quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry were used to validate dysregulated proteins. One hundred forty-six dysregulated proteins with more than twofold expressions were quantified, 22 of which were first reported to be relevant with GC. Most of them were involved in cancers and gastrointestinal disease. The expression of a panel of four upregulated nucleic acid binding proteins, heterogeneous nuclear ribonucleoprotein hnRNPA2B1, hnRNPD, hnRNPL and Y-box binding protein 1 (YBX-1) were validated by Nano-LC-MS/MS, qRT-PCR, western blot and immunohistochemistry assays in ten GC patients’ tissues. They were located in the keynotes of a predicted interaction network and might play important roles in abnormal cell growth. The label-free quantitative proteomic approach provides a deeper understanding and novel insight into GC-related molecular changes and possible mechanisms. It also provides some potential biomarkers for clinical diagnosis.
Highlights
Gastric cancer (GC) has long been recognized as among the world’s major malignancies, ranked fifth in incidence and third in mortality since 2012 [1,2,3]
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We confidently identified 146 dysregulated proteins including 22 proteins first reported on paired GC and adjacent tissues by a coupled label-free MS approach
Summary
Gastric cancer (GC) has long been recognized as among the world’s major malignancies, ranked fifth in incidence and third in mortality since 2012 [1,2,3]. Common methods for detecting GC are endoscopy and biopsy, which are both time-consuming and invasive, and can only identify the disease at a relatively late stage [8]. A better understanding of gastric carcinogenesis through proteomic and genetic studies can provide important novel insights into development and progression of GC, and can be utilized to improve early diagnostic screening and provide effective drug intervention targets [10]. These advancement can only be achieved through the use of new technologies and methods
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