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Gene Diagnostic Methods For Pancreatic Cancer In Feces

Posted on:2012-07-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y RenFull Text:PDF
GTID:1114330335459228Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Pancreatic cancer is a highly malignant tumors. In recent years, the risk of pancreatic cancer show ascendant trend worldwide. In the United States, pancreatic cancer is in the malignant tumor position 4 to the cause of death, gastrointestinal tumors is to the cause of death of the second place. In our country, pancreatic cancer has now become one of the common malignant gastrointestinal tumors. The trend of the pancreatic cancer incidence have increased year by year, however diagnosis progress was very slowly, so pancreatic resection rate is very low, surgical resection is still only 20% ~ 30%, 5-year survival rate is still below in 18 percent in the surgery, therefore, development of new screening and diagnosis methods, the comprehensive analysis of pancreatic cancer high-risk groups, and improve pancreatic cancer early diagnosis rate is to improve the prognosis of pancreatic cancer. Early pancreatic tumor diameter acuities refers to 2cm. And confined to pancreatic essence inside, no pancreas outside infiltration and lymph node metastasis. Clinically small pancreatic cancer is not early pancreatic cancer, The small pancreatic cancer is only concerned with the tumor size. Only when the pancreatic cancer is below 2cm diameters, whatever whether it transfer outside of pancreas or has the lymph node metastasis. And some scholars defined the diameter acuities below 1cm as tiny pancreatic carcinoma. Along with the rapid development of molecular biology, early diagnosis of pancreatic cancer in many aspects made important progress.Cancerous tumors have multiple genes participation in the process. Pancreatic cancer is also not exceptional, for these gene changes research provide for the early diagnosis of pancreatic cancer, the research of new molecular markers has become one of the hot spot in the research field of pancreas. Study reports pancreatic cancer related gene mainly limited to basic research, clinical research is still in the initial stage. These genes mainly includes K-ras, telomerase, DPC4 and p53 etc, the specimen sources include pancreatic tissue, pancreatic juice exfoliated cells, pancreatic duct cells brush inspection specimens, fine needle aspiration biopsy specimens, etc. Application of the simple and non-invasive method is a urgent problem to be solved to the pancreatic cancer screening currently. Our research detected the pancreatic cancer gene molecular markers (microRNA, ALU repeats, k– ras gene) in the feces which is the non-invasive testing means, and establish a suitable clinical application of high-efficiency, simple and convenient method of the diagnosis of pancreatic cancer. We extraction DNA and RNA in the feces, and established the real-time quantitative method of the the ALU repeats and PNA - PCR and microRNAs. Results show that, (1) Pancreatic cancer compared with normal controls, the express abundances of the miR - 181b, miR -196a miR - 210 increased (p < 0.05), in the diagnosis value aspect, miR - 181b and miR - 210 expression has the statistical significance. In the corelation analysis of the pancreatic cancer and clinical factors, we found miR - 196a with pancreatic tube diameter is related (r = Spearman 0.516, p= 0.041). (2) the feces ALU sequence express amount of pancreatic cancer patients higher than the chronic pancreatitis and normal controls (p< 0.05). Compare the pancreatic cancer patients with chronic pancreatitis and normal people, the diagnosis evaluation through ROC analysis, AUC-ROC is 74.8%(95% CI: 0.661-0.835),the sensitivity is 75.6% and specitivity is 67.1%,the differences have statistically significant (p < 0.05). (3) At 112 patients with pancreatic cancer patients, the mutation rate of the k-ras gene is 55.4% (62/112), 89 cases of chronic pancreatitis, its k– ras gene mutation rate is 22.4% (20 /89), both the difference is statistically significant(p < 0.05), k– ras gene for pancreatic cancer diagnosis sensitivity is 55.4% (62/112), specificity is 77.5%(69/89), there are 92 cases > 37U/ml in the serum CA199 in pancreatic cancer patients, the sensitivity of the diagnosis of pancreatic cancer is 82.1% (92/112), specificity is 86.5% (77/89), joint feces k - ras gene detection and serum tumor markers CA199 detection, the sensitivity is 87.5%, specificity is 76.4%. In the diagnosis value aspect, the combination of the K - ras gene mutations and CA199 level detection pancreatic cancer compared to CA199 alone, difference was statistically no significant (p > 0.05), but relative to it, early pancreatic cancer was statistically significant difference (p < 0.05), indicating that K - ras genes maybe has certain value on early diagnosis of pancreatic cancer.Although feces gene detects as screening method to pancreatic cancer patients has begun studied both at home and abroad, but PCR successful rate is low, the result is unstable and unreliable, it is difficult to used for large screen. We aim to improve the traditional feces DNA extraction method, improve its PCR success rate and further evaluation the value of the feces gene detectection in pancreatic cancer screening. The feces gene detection expected to become a new kind of simple, noninvasive and cheap screening method of the pancreatic cancer.
Keywords/Search Tags:pancreatic cancer, MicroRNAs, k-ras, Alu repeats, early diagonosis
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