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Study On Plasma MiRNAs Expression In The Early Stage Of Gastric Cancer

Posted on:2014-07-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:H CaiFull Text:PDF
GTID:1264330425967540Subject:Zoology
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Gastric cancer is the second most common cause of digestive oncology death, with a5-year survival rate of approximately20%. Metastasis is a complex, multi-step process in which cancer cells migrate from the primary neoplasm to a distant location, but the patients do not gain benefit from surgery or radiation therapy and chemotherapy. Specific molecules were needed for effective diagnosis to treat advanced gastric cancer, related genes and signaling pathways is very important for gastric cancer diagnosis, treatment.Gastric cancer is expressed by kinds of causes, such as abnormal expression of coding and non coding structures. Unfortunately many molecular related metastasis such as adhesive molecular, cell mobile related molecular and immune escape molecular, were not enough to explain the different levels of gastric cancer with metastasis, and a few unknown molecules that could regulate gastric cancer metastasis maybe not be reported. However, the researchers at home and abroad still focused on the coding protein transcription; therefore we maybe ignore the role of ncRNA in tumor metastasis. These ncRNAs could regulate the structure of DNA, protein translation and transcription and the expression of RNA, they could affect the physiology of human body with molecular, cell or tissue level. Certainly, this also included in a variety of diseases associated with malignant tumors of the development process. The miRNAs also regulated the pathway of molecular associated with tumor growth and some apoptosis in the form of "one to multiple". In theory, comparing to the proteins associated with tradition and metastasis, the targeted miRNAs could control and reverse transcription involves a variety of tumor metastasis related to genetic changes in phenotype effectively. In the past, it is generally accepted abnormal expression that encoding protein expression of oncogenes or tumor suppressor genes was the key link in the process of gastric cancer, and as a number of ncRNAs have been found and some of the ncRNAs play the role in regulate gene expression was solved, then exploring the relationship between miRNAs and the gastric cancer become a hot point in the recent years.This research has detected the plasma miR-106b, miR-20a and miR-221and their expression levels in patients with early stage gastric cancer and in the normal people. It aimed to explore the non-invasive biomarkers for the early detection of gastric cancer. The plasma expression levels of 15selected miRNAs (miRNA-1,-106a,-106b,-17-5p,-20a,-21,-221,-27a,-34,-376c,-378,-423-5p,-451,-486,-744) in30gastric cancer patients and30age-and gender-matched healthy controls were measured and then validated those miRNAs that differentiating gastric cancer and controls in another60patients and60matched controls using quantitative reverse transcription polymerase chain reaction. The areas under the receiver operating characteristic (ROC) curves were used to test the sensitivity and specificity of gastric cancer diagnosis using these identified plasma miRNAs.Three plasma miRNAs miRNA-106b, miRNA-20a, and miRNA-221, were significantly elevated in gastric cancer patients than in healthy controls (P<0.05). Furthermore, the areas under the ROC curves using miR-106b, miR-20a, and miR-221for gastric cancer diagnosis were0.7733(95%CI,0.7758-0.8409),0.8593(95%CI,0.8046-0.9139), and0.7960(95%CI,0.7256-0.8664) respectively. Furthermore, these three miRNAs had a statistically significant elevation in gastric cancer patients compared with healthy controls at each of the four stages. However, there were no significant differences in the plasma levels of the three miRNAs among the four TNM stages (P>0.05).The conclusions of this study are as follows,(1) By qRT-PCR detection technology could validate the plasma of patients with the early gastric cancer, miRNA-106b, miRNA-20a and miRNA-221were highly expressed, and the result do not contact with age, gender, histological type and lymph node metastasis, there were no significant differences;(2) In different clinic stages, miRNA-106b, miRNA-20a and miRNA-221had expresses highly compared with healthy controls, but the expression levels with these three miRNAs were not significant differences;(3) The curve of ROC analysis prompt that plasma miRNA-106b, miRNA-20a and miRNA-221combination detection have a greater AUC value, and a higher value could prompt early diagnosis for gastric cancer, which suggesting that these three plasma miRNAs could be used as the biomarkers for early detection of cancer.
Keywords/Search Tags:Gastric cancer, plasma, miRNAs, Biomarker, Early detection
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