CXCL1 As A Putative Tumor Marker For Gastric Cancer Progression

BackgroundGastric cancer is one of the most common malignant tumors in the world. In China, the incidence and mortality rate ranks first three in a variety of malignant tumors. While radical surgery is the only potentially curative method for localized disease with 5-year survival rate of 20%-30%%. Moreover, the radical surgery rate only 50%. Because gastric cancer (GC) is heterogeneous and current tumor markers are limited to be practically applied, finding molecular markers that are able to predict the potential of tumor progression is important for appropriate individualized therapy.Cancer Metastasis Research Center (CMRC) has collected gene expression and copy number profiles of gastric cancer and its adjacent normal tissues by 17K cDNA microarray. With this high-throughput database, we had published several studies related to gastric cancer biology. For the current study, we raised up the number of gastric cancer tissues and their gene expression profiles to identify the novel molecular candidates for gastric cancer prognostic marker. CXCL1, the chemokine growth-regulated oncogene 1, is one of a number of chemokines of the CXC family which promote chemotaxis of granulocytes and endothelia. CXCL1 was first identified in 1985 as an autostimulatory melanoma mitogen from the human malignant melanoma cell line. CXCL1 has been studied for cancer biology fields because of its relationship with cell growth, angiogenesis, and metastasis in various cancer types. Overexpression of CXCL1 in immortalized melanocytes results in cell transformation. CXCL1 is a potent mediator of tumor-associated angiogenesis in Kaposi's sarcoma and non-small cell lung cancer, and its expression is associated with increased density of leukocytes and blood vessels in mice model. However, the role of CXCL1 in gastric cancer has not been reported.We identified differentially expressed genes between 96 cancer and 98 normal gastric tissues using Significant Analysis of Microarray (SAM). Among them, more than 2-fold overexpressed genes in tumor tissues which encode secreted proteins were selected. With Ingenuity Pathway Analysis, we found 34 genes related to cancer. with In our analysis, a variety of tumor progression-related chemokine CXCL1, closely related with the occurrence of gastric cancer invasion and metastasis. The selected gene was validated with ELISA assay using sera of 96 GC patients and 48 healthy donors. CXCL1 concentrations in serum samples of GC patients were significantly elevated compared with healthy donors. Within GC patients, CXCL1 serum levels were increased according to the tumor stage and lymph node metastasis. These findings provide that CXCL1 could be a candidate marker for gastric cancer progression. In this study, it has 2 parts.Part1 Application of oligonucleotide microarray to analysis the gene level of gastric cancerAim:To detect the differentially expressed genes between normal and tumor gastric cancer, and the effct of the differential gene in tumor occurrence and developmentMethods:The Gene chip technology was used in this study.Results:There exists an obviously different genes in Gastric cancer tissue and normal gastric tissue. Among these different genes,29 genes related to tumor,18 genes have the relationship with the malignant degree,15 genes were associated with tumor cell death, 13 genes were related with tumor development process; in addition,12 genes associated with tumor invasion,11 genes associated with tumor proliferation,9 genes were related with tumor growth,8 genes were related cell movement,7 genes were related with cell division, and 5 kinds of genes related with tumor angiogenesis,3 genes,2 genes and 2 genes were related with cellcycleprogression, transformation, and differentiation respectively.Conclusion:cDNA microarray is an efficient and fast screening approach of gastric cancer and metastasis-related genes; compared with normal gastric tissue, gastric tissue has several differences in gene expression; the expression of tumor-associated different genes increased in gastric cancer, coordinated the role of these genes may have a effection of the occurrence and development of gastric cancer; CXCL1 is one of the novel tumor related gene of gastric cancer. Part2 CXCL1 levels in serum of gastric cancer and the relationship between lymph node metastasisAim:To validate the CXCL1 levels in serum of gastric cancer patients, and the relationship between CXCL1 and gastric cancer staging and lymph node metastasis.Methods:We used ELISA in our experiment.Results:We found that CXCL1 concentrations in the sera from gastric cancer patients were elevated (mean,146.6 pg/ml) compared with those of the normal controls (98.2 pg/ml) (p<0.001). CXCL1 concentrations in stage 1B,3A,3B, and 4 were significantly higher than normal (p<0.05). Within gastric cancer patients, the concentrations in stage 1B,3B, and 4 were higher than 1A, and stage 4 was the only one that were elevated compared with stage 2 with significance (p<0.05). We noted that the concentration of CXCL1 in sera of gastric cancer patients was significantly higher in advanced gastric cancer than early stage. There was positive correlation coefficient (r=0.29) with significance (p=0.004) between CXCL1 concentrations and the numbers of lymph node metastasis by Pearson correlation coefficient.Conclusion:CXCL1 expression in serum level has a positive correlation with gastric cancer progression and lymph node metastasis; CXCL1 expression in serum level will be as a putative tumor marker for gastric cancer progression.Conclusion of the whole study:1,cDNA microarray is an efficient and fast screening approach of gastric cancer and metastasis-related genes; 2,Compared with normal gastric tissue, gastric cancer tissue has several differences in gene expression; the expression of tumor-associated different genes increased in gastric cancer;3,Coordinated the role of these genes may have a effection of the occurrence and development of gastric cancer;4,CXCL1 expression in serum level has a positive correlation with gastric cancer progression and lymph node metastasis;5,CXCL1 expression in serum level will be as a putative tumor marker for gastric cancer progression.