<i>LYZ</i> and <i>SST</i> Prevent the Progression of Chronic Inflammation into Adenocarcinoma in the Stomach

Abstract

Background: The transformation of chronic inflammation into adenocarcinoma in stomach lacks specific molecular markers to monitor early cancer development and effective drugs for early intervention. In this study, we identified two key genes, LYZ (encoding lysozyme) and SST (encoding somatostatin). Methods: LYZ and SST was identified by integrating high-throughput sequencing data derived from patients related to gastritis-cancer and microarray data of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Their expression was verified in human specimens and rat model of gastritis-cancer. The clinicopathological significance study for predicting the progression of chronic gastritis to cancer transition and cancer prognosis was using ROC curve, survival and correlation analysis. Their expression difference was tested in patients those received effective interventions, based on a multicenter randomized control clinical trial for precancerous disease in stomach. Findings: LYZ and SST were consistently downregulated in the process of chronic inflammation into adenocarcinoma in stomach. The ROC curves of these genes had a great value in predicting precancerous disease and gastric cancer independently and in combination. Their expression levels were correlated with gastritis and intestinal metaplasia staging, and would increase after effective intervention in precancerous patients. Interpretation: We identified LYZ and SST as key “hub” genes for chronic gastritis to cancer transition, promising biomarkers of significant clinical predictive value, and potential targets for inhibiting gastric cancer development. Trial Registration: ChiCTR-IOR-16008027 Funding Statement: National Natural Science Foundation of China (No.81703931, 81973819) Natural science foundation of Guangdong province in 2017 (2017A030310121) Natural science foundation of Guangdong province in 2019 (2019A1515011145) Breakthrough Project of TCM Dominant Diseases with Special Funds for Strengthening Traditional Chinese Medicine in 2015 (No.19), Guangdong Administration of Traditional Chinese Medicine. Major Projects of First-Class Disciplines in Guangzhou University of TCM in 2018 (A1-AFD018181A27). Major Research Projects of Guangzhou University in TCM in 2019 (A1-2606-19-110-007). Innovative Research Team Project of Innovation Hospital in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in 2017 (2017TD05). Youth Scientific Research Talents Training Program of Innovation Hospital in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in 2015 (2015QN09). The Second Batch of Clinical Research Program of Innovation Hospital Phase II project in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in 2019 (2019IIT19). Declaration of Interests: The authors declare no conflicts. Ethics Approval Statement: The ethics committee of the first affiliated hospital of Guangzhou University of Traditional Chinese Medicine approved this study (approval number ZYYECK [2015]024-ND-01, ZYYECK [2017]023-XZ-01, ZYYECK [2019]015). The ethics committee of the first affiliated hospital of Guangzhou University of Traditional Chinese Medicine approved this study (approval number ZYYECK [2015]024-ND-01). The rat study design and protocol were approved by the animal ethics committee of Beijing University of Chinese Medicine, China (No. BUCM-4-2018060403-2007).