Ying Zhu1, Wen Xu1, Wei Hu1, Fang Wang1, Yan Zhou2, Jianguo Xu3, Wei Gong4. 1. Department of Gastroenterology, Shenzhen Hospital of Southern Medical University, Shenzhen, 518000, Guangdong, China. 2. Information Management Section, Bethune International Peace Hospital, Shijiazhuang City, Hebei Province, China. 3. Department of Liver Disease Center, Shenzhen Hospital of Southern Medical University, Shenzhen, 518000, Guangdong, China. xujianguo1@smu.edu.cn. 4. Department of Gastroenterology, Shenzhen Hospital of Southern Medical University, Shenzhen, 518000, Guangdong, China. drgwei@foxmail.com.
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).
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 PHGpatients before and after endoscopic cyanoacrylate injection, using label-free quantitative (LFQ) mass spectrometry, to identify potential biomarker candidates in gastric mucosa from PHGpatients 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 PHGpatients 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).
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