The Urinary Protein Biomarker And The Gene-Environment Interaction Of Gastrointestinal Tumors

Colorectal cancer(CRC)and gastric cancer(GC)are the major types of gastrointestinal tumors.The incidence of CRC and GC in China is the fifth and second in male,and the fourth and third in female.The tendency of CRC incidence in China shows an increasing trend and more than one-third of patients will develop liver metastasis.At present,the screening and monitoring methods for CRC and CRC with liver metastasis including colonoscopy,ultrasound detection,etc.,but these methods are expensive and not conducive to a wide range of screening.At the same time,the sensitivity and specificity of serum markers are not ideal.Urine is a kind of body fluid that can be collected in a non-invasive manner,which contains a large number of proteins from the body and can work as a good source of disease marker researching.In this study,quantitative proteomics strategies were used to identify urinary proteins.We divided the samples into 4 groups according to the disease progression,healthy control(HC),CRC without metastasis,CRC with lymph node metastasis(CRC-LNM)and CRC with liver metastasis(CRC-LM),each group contains 9 samples.The tandem mass tags(TMT)kit was used to label the samples in each group.And then the differentially expressed proteins were quantitatively identified via 2D-LC-MS/MS strategy.One of differentially expressed protein,hepatocyte growth factor-regulated tyrosine kinase substrate(HGS),was selected to preliminary functional studies according to the proteomic analysis and the previous work in our lab.The results showed that using the NC membrane enrichment method,300-800?g urinary proteins were enriched from 40mL urine samples from healthy individuals and CRC patients.The molecular weight of urinary proteins is between 20 and 130kDa,showing good quality.There were 995 common proteins in the four groups,and the differential proteins were enriched in the cell apoptosis and proliferation pathways.The differential protein HGS was related to the cell migration ability and may be a potential biomarker of CRC liver metastasis.The carcinogenesis of GC is the result of multiple factors for a long time.Genes and the environment can affect the risk of gastric cancer.Seven single nucleotide polymorphisms(SNPs)were identified in the four major gastric cancer-related genome-wide association study(GWAS),suggesting that genetic factors have a certain role in the development and progression of gastric cancer.At the same time,Helicobacter pylori(H.pylori)infection,smoking and drinking are important environmental factors related to gastric cancer.The aim of this study was to explore the gene-environment interaction in GC and to study the effects of seven susceptible loci and H.pylori infection,smoking and drinking on gastric cancer and severe intestinal metaplasia/dysplasia(severe IM/dysplasia).The study found that PSCA rs2294008/rs2976392 showed a significant,multiplicative interaction with H.pylori infection in risk of GC.Meanwhile,PRKAA1 rs13361707 had an additive interaction with H.pylori infection.SLC52A3 rs13042395 showed an interaction with alcohol drinking in risk of GC.Moreover,three SNPs,MUC1 rs4072037,ZBTB20 rs9841504 and PRKAA1 rs13361707,were associated with precancerous gastric lesions.The study suggested that genetic predisposition factors identified by GWAS may interact with environmental risk factors,Particularly for H.pylori infection and alcohol consumption,to increase the risk of GC.