| Gastric cardia adenocarcinoma (GCA) is one of the most frequent digestive malignant diseases in Linzhou, Henan province, northern China. Recent studies by us and other laboratories indicate a remarkable epidemiological characteristic for GCA is the occurring together with esophageal cancer (EC) in the same high-incidence area (HIA). GCA and EC still the leading of cancer-related deaths in these areas. There are several distinct differences between GCC and distal gastric cancer with respect to epidemiology, etiological factors, histogenesis and clinical characteristics, and therefore GCA should be catergorized as a distinct clinical disease. The 5-year survival rate for GCA at the advanced stage is only 10 percent. However, the 5-year survival rate for GCA in the early stage GCA for GCA could be as high as 90%. However, more than 80% of the GCA patients are at the advanced stage when diagnosed at first in clinc, which is the leading cause of stable mortality parrent for GCA. Lacking of biomarker for high-risk subject screening and early detection for GCA is the leading cause for the late diagnosis and stable mortality of GCA. Apparently, it is crucial to elucidate the molecular mechanism of GCA multiple stage carcinogenesis, to select and identify the close related protein and gene to GCA, and to establish the biomarkers for high-risk subject screening and early diagnosis,especially useful for the large-scale population screening with noninvasive, enconmic and easy technique for decreasing the incidence and increasing the survival rate for GCA, which is one of the specific aims in our study.The recent studies suggest: that Ras association domain family A gene (RASSF1A) is one of the new candidates of tumor suppressor genes and it has been well recognized that may be one of important candidates for high-risk subject screening and early diagnosis. RASSF1A methylation is common molecule event in lung and nasopharyngeal cancers. Biologically, it is characterized: (1) RASSF1A methylation occurs rarely in the normal tissue, but, with a high frequency in cancer tissue more than 90%(liver cancer); (2) the subject with precancer with RASSF1A methylation have been identified to develop into cancer(breast and lung); (3) being one of important candidate biomarkers for high-risk subject screening and early diagnosis, RASSF1A methylation could be detected easily in body fluid(blood, sputum, urine) obtained from noninvasive technique, which is economic and easier. Obviously, to characterize the alterations of RASSF1A methylation in the normal, precancerous and cancerous tissues is of crucial theoretical and clinical application in understanding the mechanism of GCA and establishing biomarker for high-risk subject screening and early diagnosis. However, the studies on the relationship between the RASSF1A methylation and gastric cardia carcinogenesis have not been reported. Thus, the present study was undertaken to determine RASSF1A methylation and mRNA expression in the cancer and adjacent cancer tissue to further understand the moleculer mechanism of GCA and to provide theoretical basis for establishing the biomarkers to screen the high-risk subjects and to make early diagnosis for GCA.Materials and methods:In this case-control study,42(22 from man and 20 from woman,52.00±7years old) surgically resected adenocarcinomas of gastric cardia come from Linzhou (originally Linxian), the high-risk area of esophageal cancer in Henan, China. Adjacent cancer tissues and carcinoma tissues were selected from every subject. All the subjects wereundergone endoscopic biopsy examination. Reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP) were undertaken to determine the expression and methylation of RASSF1A inGCA. The x2 test were used for the statistics, P<0.05 was considered significiant.Result:(D Expression of RASSF1A mRNA were presented in 41 of 42of adjacent cancer tissues,however,loss of RASSF1A mRNA expression were found in 31 cases (74%)in primary tumor(p< 0,05)(2) Promoter methylation of RASSF1A occurs 64% in tumor, but, with only 2% in adjacent cancer tissue(3) All the GCA cases with promoter gene methylation showed loss expression of RASSFlAmRNAConclusions:There is close relationship between expression of RASSFlAmRNA and carcinogenesis of GCA. Loss expression of RASSF1A gene was caused by methylation of the gene promoter, which was the possible molecular mechanism of GCA and might be a frequent molecular event in GCA. Thus, RASSF1A methylation could serve as a useful biomarker to screen the high-risk subjects and to make early diagnosis for GCA... |
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