Circulating DNA And K-ras Gene Mutation For Diagnosis And Prognosis By Integrative Oncology In Advanced Pancreatic Cancer

IntroductionPancreatic cancer is a common malignant tumor in digestive system.There has been a significant increasing trend in the incidence of pancreatic cancer.The prognosis of andvanced pancreatic cancer is depressed,and the whole 5-year survival rate is only 5 percent.Resistance of pancreatic caner cells by most of the chemotherapeutic agents and radiation led to the unsuccess of modern medicine in the management of the disease and a very dismal prognosis.Former researches indicated that QYHJ traditional Chinese medicine(TCM) had showed some advantages in pancreatic cancer treatment.Recently,the relationship between prognosis and gene in pancreatic cancer is emphased.More and more research exposed the significance of the circulating DNA and K-ras gene mutation for the diagnosis and prognosis of cancer.ObjectiveThis study is to explore the relationship between the circulating DNA and K-ras gene mutation for the integrated traditional Chinese and western medicine in advanced pancreatic cancer.And the potential mechanism of Qingyihuaji formula (QYHJ) in the treatment of pancreatic cancer.MethodsPartⅠ:From May 2002 to Sep 2008,289 advanced pancreatic cancer patients confirmed by cytology or histology were selected from patient database. Kaplan-Meier method was used to calculate the survival and Log-rank test was used to compare the differences between groups.A multifactorial Cox proportional hazard model analysis was introduced to examine the prognostic factor in patients with inoperable advanced pancreatic cancer.According to these prognostic factors which had statistics significance,we established prognostic index(PI) equation. PartⅡ:Forty healthy controls,91 patients with advanced pancreatic cancer and 28 patients with suspected pancreatic masses were included in present study.DNA from plasma was extracted.The quantitation of the plasma DNA were performed by a quantitative fluorescence-based assay by using SYBR greenⅠ.Point mutation of K-ras gene was analyzed by using genie sequencing.ROC(relative operating characteristic) curve was derived by circulating DNA.The value of the the circulating DNA and K-ras gene mutation in the advanced pancreatic cancer was calculated by chi square test.PartⅢ:From Aug 2007 to Sep 2008,DNA and K-ras gene mutation from plasma of 91 advanced pancreatic cancer patients were examined.Kaplan-Meier method was used to calculate the survival and Log-rank test was used to compare the differences between groups.A multifactorial Cox proportional hazard model analysis was introduced to examine the prognostic factor in patients with inoperable advanced pancreatic cancer.ResultsPartⅠ:The retrospective study on 289 patients with advanced pancreatic cancer showed the median survival time of 6.8 months and overall half,1,3 and 5 years survival of 22.1%,6.3%and 3.7%.Multivariate analysis showed the correlation of survival with KPS＜80,serum CA199≥500 U/ml,abnormality of carbohydrate tolerance,pain,abdominal dropsy,GGT≥110ug/ml,emaciation,hepatic metastasis, QYHJ herbs and operation style(P＜0.05).PI was established according these factors. With the increasing of PI,the survival time showed a tendency of decline.PartⅡ:As a new tumor mark,circulating DNA can diagnosis the metastatic pancreatic cancer.With the high specificity and positive predictive value,K-ras gene mutation was also a good tumor mark for pancreatic cancer.If we use K-ras gene mutation and circulating DNA together,the sensitivity of diagnosis would be improved,so they can be used as an auxiliary diagnosis for advanced pancreatic cancer.PartⅢ:The retrospective study on 91 patients with advanced pancreatic cancer showed the median survival time of 7.4 months and overall 1 and 2 years survival of 27.1%and 13.1%.The circulating DNA and K-ras gene mutation can be used as new prognosis marks.The patients with high level expression of circulating DNA or K-ras gene mutation will have a very dismal prognosis.The integrated traditional Chinese and western medicine in advanced pancreatic cancer is benefit for the patients with wild type K-ras gene.Conclusion1.Clinical research showed that the integrated traditional Chinese and western medicine in advanced pancreatic cancer may benefit to advanced pancreatic cancer patients by stabilizing tumors and prolonging life expectancy.KPS＜80,serum CA199≥500 U/ml,abnormality of carbohydrate tolerance,pain,abdominal dropsy, GGT≥110ug/ml,emaciation,hepatic metastasis,QYHJ herbs and operation style may be important prognostic factors for advanced pancreatic cancer patients.2.K-ras gene mutation and circulating DNA can be used as an auxiliary diagnosis for advanced pancreatic cancer.They also can be a new tumor mark to diagnose the metastatic pancreatic cancer.3.The circulating DNA and K-ras gene mutation can be used as a new prognosis mark for advanced pancreatic cancer.The patients with high level expression of circulating DNA or K-ras gene mutation will have a very dismal prognosis.They may be important prognostic factors for advanced pancreatic cancer patients.