Discovery and validation of novel protein markers in mucosa of portal hypertensive gastropathy

Abstract

Background Portal 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. Methods We 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. Results LFQ analyses identified 423 significantly differentially expressed proteins. 17 proteins that significantly elevated in the gastric mucosa of PHG patients were further validated using PRM. Conclusions This is the first application of an LFQ-PRM workflow to identify and validate PHG–specific 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).

Serum proteomic profiling of patients with compensated advanced chronic liver disease with and without clinically significant portal hypertension

“…One study used proteomic profiling of gastric mucosa samples from patients with endoscopic finding of portal gastropathy, and healthy individuals, and they identified 17 differently expressed proteins in the portal gastropathy group, with the most prominent being tenascin-C (TN-C) and fibulin-5. These proteins relate to angiogenesis and lymphangiogenesis, as the adaptive and compensatory mechanisms activated along the PH development [ 9 , 11 , 12 ]. Osborn et al have compared the serum proteomic profiles of children with biliary atresia and identified five protein candidates (SEMA6B, SFRP3, COMMD7, BMX, and VCAM1) in children with clinical signs of CSPH [ 13 ].…”