Clinical And Genetic Factors Predicting Malignant And Premalignant Lesions In Gastric Carcinogenesis

Gastric cancer is a common malignant tumor. Althought its incidence and mortality has an obvious decrease in the past 70 years, it is still a disease with poor prognosis and high mortality and it has a second cancer related death rate worldwide. About 50% of gastric cancers happen on the basis of premalignant diseases such as atrophic gastritis; the diagnositic rate of early gastic cancer is about 6%-20%, and for the advanced gastric cancers, 5-year survival rate is only about 5%-15% even the patients accept radical surgery, and at least more than a half advanced gastric cancer undergo pallitive surgery whose average survival time is less than 6 months. So early diagnosis, early treatment will help to improve the possibility of surgery dissection and the prognosis. Accurate judgement of premalignant lesions to malignant lesions with suitable treatment will be of great importance for human beings.The present classification systems of gastric cancer based on pathology are failed to efficiently predict the risk of sequential development from premalignant lesions such as intestinal metaplasia and even dysplasia to malignant lesions. Recent studies of molecular biology have revealed that certain gene alterations might have associations with some premalignant lesions. For example, mutation in p53 gene was detected in intestinal metaplasia lesions adjacent to gastric tumors. Overexpression of cyclooxygenase-2 was detected in intestinal metaplasia-associated gastritis as well as gastric cancer. Boussioutas et al examined the expression profile of 124 gastric mucosa samples including gastritis, intestinal metaplasia, and adenocarcinoma and found a series of genes were probably related with tumor progression.However, there are no good biomarkers that help to efficiently diagnose early-stage gastric cancer. Besides, we also lack of molecular epidemiology research data about premalignant lesions of stomach. The already existing informatiion can not be used for clinical diagnosis. So to study the differences and relationship between gastric cancer and premalignant lesions and to find out cancerative molecular information premalignant lesions will be of high evaluation.We collected tissue samples and clinical information of gastric cancer, premalignant lesions and superficial gastritis. Affymetrix Huamn Genome U133 plus2 oligonucleotide microarray technique was used for detection of differential expression profile of gastric cancers, premalignant lesions and superficial gastritis and we screened differential expressive gene subset and found possible related biological pathway using different kinds of bioinformatics methods such as SAM ( Significance analysis of microarray ),R,SVM( Support vector machine Heave one out and GENMAPP software. Then quantitative RT-PCR and in situ hybridization were used for verification of some pathway involved collagen genes. Based on the result of oligonucleotide microarray, a possible gastric cancer predictive formula was established and the formula was valued and confirmed using the data downloaded from the NCBI GEO database.In conclusion, we successfully established a tissue bank and clinical material and pathological material follow up data base for gastric cancer and premalignant lesion patients which can be used for clinical primary prevention of gastric cancer. And we found subsets of genes that could separate gastric cancer and premalignant lesions and function annotation was also carried out. We also found a focal adhesion related biological pathway, and pathway related subsets of extracelluar matrix and collagen. And these subsets of genes could also separate gastric cancer and premalignant lesions effeciently. Verification of the pathway involved genes further indicated that collagen genes expression profile could be potential classifer of gastric cancer. GS003 was found, and it was a premalignant lesion with the same alteration at molecular level, but not at pathological level, as malignant lesion. This type of lesion may represent a transitional phase from premalignant status to malignant status. Possible gastric cancer predictive formulas was established and validated with downloaded NCBI GEO data, and got a 80% consistent rate..