| Background and ObjectivesGastric cancer is one of the most common malignancies, and its incidence is in the fourth place behind cancerous of the lung, breast, colon and rectum, with an estimated 934,000 new cases per year. Although its incidence has been declining in many countries, it is still the second cause of cancer mortality, accounting for 700,000 deaths worldwide in 2010. Almost two-thirds of the cases occur in developing countries and 42% in China alone. It is a severe threat to peoples health.In a multistep cascade, chronic gastritis progresses through premalignant stages of atrophic gastritis, intestinal metaplasia and dysplasia, to eventually gastric cancer. As symptoms are often absent or non-specific in patients with an early stage of disease, gastric cancer is usually diagnosed at an advanced stage. Premalignant gastric lesions are well known risk factors for the development of intestinal type gastric adenocarcinomas. The progression of premalignant gastric lesions to gastric cancer generally takes decades and may thus provide a basis for cancer prevention by early intervention, and potentially also for early detection and treatment of advanced precursors and gastric carcinomas.Recent studies have found that ornithine decarboxylase has a hign expression in many tumors, which has attracted wide attention. Ornithine decarboxylase(ODC) is the first-rate limiting enzyme in the polyamine biosynthesis pathway. By regulating the level of polyamine, ODC plays an important role in the differentiation and proliferation of cell and the generation and development of cancer. Large number of studies show that ODC has a close relationship with gastric carcinoma,c-myc gene was found to be the cellular homolog of retroviral v-myc oncogene about 30 years ago. It is located on chromosomal region 8q24, has 3 exons and encodes a nuclear phosphoprotein. It is an important regulator of proliferation, differentiation and apoptosis. c-myc has been described as a key element of several carcinogenesis processes in humans. Many studies have shown an association between c-myc deregulation and gastric cancer.The correlation of ODC and c-myc in precancerous gastric lesions tissues has a less research. In our study, we detected the expression of ODC and c-myc in chronic superficial gastritis, intestinal metaplasia, atypical hyperplasia and gastric carcinoma, to analyse the differences and relevance of the two, and to explore the correlation and significance of the expression of ODC and c-myc in gastric carcinoma and precancerous lesions.Materials and MethodsA total of 78 gastric mucosal biopsy specimens, including 18 chronic superficial gastritis (CSG),30 gastric cancer(GC) and 30 gastric precancerous lesions [chronic atrophic gastritis with intestinal metaplasia (CAG with IM, n= 18) and dysplasia (DIY, n=12)] were studied using RT-PCR and immunohistochemistry. The study was performed in the Second Affiliated Hospital of Zhengzhou University between 2009 and 2010. GC tissues could be further separated on the basis of differentiation grade. Histopathologically, all the 30 gastric specimens were confirmed as adenocarcinoma. The tumors were histologically graded as well-differentiated(9 patients), moderately-differentiated(5 patients) and poorly-differentiated(16 patients). All of the biopsies were taken from gastric antrum. All patients had complete endoscopic and pathological diagnosis. The expressions of ODC and c-myc were detected by RT-PCR and immunohistochemistry at different stages of gastric carcinogenesis, to explore the correlation between ODC and c-myc and their relationship with precancerous gastric lesions. Results1. The expression of ODC mRNA increased significantly from CSG, CAG with IM, DYS to GC (0.124±0.023,0.840±0.087,0.859±0.083,0.900±0.095,P<0.01). The expression of ODC in CAG with IM, DYS and GC was significantly higher than that in CSG(P<0.01). No difference of ODC mRNA expression was found among CAG with IM, DYS and GC.2. The expression of c-myc mRNA was 0.207±0.019,0.438±0.038,0.764±0.083, 0.805±0.085, in cases with CSG, CAG with IM, DYS and GC, respectively (P<0.01). The expression of c-myc was significantly higher in GC comparing with CSG and CAG with IM (P<0.01), but there was no difference between GC and DIY.3. The positive rate of ODC protein expression was 33.3%,77.8%,88.3% and 90.0% in cases with CSG, CAG with IM, DYS and GC, respectively(P<0.01). The positive rate of c-myc protein expression was 0%,33.3%,83.3% and 86.7% in cases with CSG, CAG with IM, DYS and GC, respectively(P<0.01). The positive rates of ODC and c-myc expression increased in the order of CSG<CAG with IM<DYS and finally, GC. In addition, ODC and c-myc positive immunostaining rates were significantly higher in poorly-differentiated GC than in well-differentiated GC (P<0.01).4. The expression of ODC was positively correlated with c-myc at different stages of gastric carcinogenesis(r=0.424, P<0.01), while the expressions of ODC and c-myc in both protein and mRNA were consistent.Conclusions1. The expression of ODC is positively correlated with the degree of malignity of gastric mucosa and development of gastric lesions. This finding indicates that ODC may be used as a good biomarker in the screening and diagnosis of precancerous lesions.2. The positive rate of c-myc in DIY and GC is significantly higher than that in CSG, suggesting that c-myc may play an important role as a carcinogenic factor and early gastric carcinogenic molecule during gastric carnogenesis.3. The positive relation between over-expression of ODC and c-myc implicates that both are involved in the gastric carcinogenesis. c-myc may induce the high expression of ODC, which may participate in gastric carcinogenesis. Detecting both markers together may be helpful in early diagnosis of gastric carcinoma. |
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