Abstract
BackgroundPortal hypertension induced esophageal and gastric variceal bleeding is the main cause of death among patients of decompensated liver cirrhosis. Therefore, a standardized, biomarker-based test, to make an early-stage non-invasive risk assessment of portal hypertension, is highly desirable. However, no fit-for-purpose biomarkers have yet been identified.MethodsWe conducted a pilot study consisting of 5 portal hypertensive gastropathy (PHG) patients and 5 normal controls, sampling the gastric mucosa of normal controls and PHG patients before and after endoscopic cyanoacrylate injection, using label-free quantitative (LFQ) mass spectrometry, to identify potential biomarker candidates in gastric mucosa from PHG patients and normal controls. Then we further used parallel reaction monitoring (PRM) to verify the abundance of the targeted protein.ResultsLFQ analyses identified 423 significantly differentially expressed proteins. 17 proteins that significantly elevated in the gastric mucosa of PHG patients were further validated using PRM.ConclusionsThis is the first application of an LFQ-PRM workflow to identify and validate PHGāspecific biomarkers in patient gastric mucosa samples. Our findings lay the foundation for comprehending the molecular mechanisms of PHG pathogenesis, and provide potential applications for useful biomarkers in early diagnosis and treatment.Trial registration and ethics approval: Trial registration was completed (ChiCTR2000029840) on February 25, 2020. Ethics Approvals were completed on July 17, 2017 (NYSZYYEC20180003) and February 15, 2020 (NYSZYYEC20200005).
Highlights
Portal hypertension induced esophageal and gastric variceal bleeding is the main cause of death among patients of decompensated liver cirrhosis
Clinical sample information In this study, we evaluated the application of label-free mass spectrometry and parallel reaction monitoring (PRM) to identify and validate promising biomarkers for assessing the severity of portal hypertension (PH) in decompensated liver cirrhosis patients
Most of the need lies in the detection of liver cirrhosis patients at risk of occurrence and the progression of PH, and early diagnosis and treatment may greatly contribute to enhancing the survival of such patients
Summary
Portal hypertension induced esophageal and gastric variceal bleeding is the main cause of death among patients of decompensated liver cirrhosis. A standardized, biomarker-based test, to make an earlystage non-invasive risk assessment of portal hypertension, is highly desirable. According to Portal Hypertensive Bleeding in Cirrhosis: Risk Stratification, Diagnosis, and Management: 2016 Practice Guidance by the American Association for the. Study of Liver Diseases [2], platelet count, ultrasound, transient elastography (TE), computed tomography (CT), or magnetic resonance imaging (MRI) are suggested as non-invasive methods to evaluate the severity of cirrhosis and PH. There remains a clinical need for new biomarkers that achieve quantified, inexpensive, and minimally invasive testing to assess the severity of PH
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