KRAS Mutation In CtDNA Can Predict Independently The Prognosis Of Pancreatic Cancer Patients

Research purpose and contentPancreatic carcinoma is a common digestive system tumor that has high malignant degree and is related with poor prognosis.The 5-year survival rate of pancreatic carcinoma is only 3%-6%.This is the reason why it is worthy of the name"The king of carcinoma”.In China,the incidence of pancreatic cancer has increased proximately six-fold in the past 20 years,ranking sixth in mortality rate of malignant tumors.The prognosis of each pancreatic carcinoma patient varies greatly.And radical resection and chemotherapy can affect the prognosis of cancer patients.So,we investigate whether KRAS mutation can predict disease progression and overall survival independently of other clinical factors in patients diagnosed with pancreatic cancer after radical resection and standardized postoperative chemotherapy.Methods1.Blood sample and clinical data collection:the research recruited 61 cases of pancreatic cancer patients who were underwent radical resection and standardized postoperative chemotherapy in Tianjin Medical University Cancer Hospital from March 2016 to March 2017.Peripheral blood samples were collected in EDTA test tube to extract CA199 and ctDNA.All samples were processed after extraction.The research was approved by Tianjin Cancer Institute and Ethics Committee.And the enrolled patients were followed up for 2 years.2.The extraction of ctDNA:QIAamp Circulating Nucleic Acid kit（German,QIAGEN company）is used for plasma circulating DNA extraction.3.KRAS mutation detection:human KRAS mutation detection kit（China,YZYBIO company）was used to exterminate KRAS mutation sites of various samples after quantitative analysis of extracted DNA.4.The relevant data was analyzed by SPSS 22.0 statistics software and Graphpad software.The correlation between KRAS in ctDNA mutation and clinical characteristics was determined by Chi-square test or Fisher’s test.Kaplan-Meier method was used to univariate survival analysis of OS and PFS.Multivariate analysis evaluates the effects of KRAS mutation and other co-variables on PFS and OS by Cox regression models.Results:A total of sixty-one patients were recruited with 14 months of median survival.The KRAS mutation rate in ctDNA was 34.4%.While,we found that KRAS mutation in ctDNA is not related to any clinicopathologic parameters including tumor size,lymph node status,except for clinical stage.Univariate and multivariate analysis showed the risk of significantly shortened progression-free survival（PFS）and overall survival（OS）related to ^mutKRAS ctDNA-positive and stage,including clinical stage and pathological stage.^mutKRAS ctDNA can be used as a blood biomarker to predict disease progression and death and to further risk stratification of stage IIB/III patients.Conclusions:^mutKRAS ctDNA can stratify the prognosis of PC patients.Further supplementation of TNM staging by the addition of liquid biopsy ctDNA allows for a more accurate assessment of patient prognosis.And ctDNA KRAS results can screen out patients who have poor prognosis after radical resection and standard chemotherapy,suggesting that such patients are in a high-risk state.Clinical doctors need to pay more attention to progression of disease.Considering for difference of individuals,the doctors can choose neoadjuvant chemotherapy for borderline resectable pancreatic tumor and adjust postoperative adjuvant treatment strategies appropriately.