Clinicopathological Features And Outcomes Of Pancreatic Cancer/Hsa_circ₀007564:A Novel Diagnostic And Prognostic Marker For Pancreatic Cancer

Prognosis of pancreatic cancer is extremely unfavorable.However,prognostic factors remain largely undefined.Comprehensive analyses of clinicopathologic characteristics,laboratory parameters,and treatment protocols to explore their role as prognostic factors in pancreatic cancer survival.Patients diagnosed with pancreatic cancer and hospitalized at the China National Cancer Center between April 1,2006 and May 31,2016 were included in this retrospective cohort study.Clinicopathologic characteristics,laboratory parameters,and treatment protocols were compared among patients in different disease stages.The impact of these factors on overall survival?OS?was analyzed with the Kaplan-Meier method and Cox proportional hazards model.The prognose evaluation value of compound index was assessed by univariate Logistic regression and receiver operating characteristic curve.In this study including 1433 consecutive patients with pancreatic cancer,125?8.7%?,157?11.0%?,584?40.8%?,524?36.6%?,and 43 patients?3.0%?were in stages I,II,III,IV,and unkown stage,respectively.Among these patients,272 patients?19.0%?received tumor resection,351 patients?24.5%?received systemic chemotherapy,277 patients?19.3%?received intraoperative radiotherapy,250 patients?17.4%?received interventional therapy,98 patients?6.8%?received concurrent chemoradiotherapy,and 55 patients?3.8%?received extracorporeal radiotherapy.Median OS was 10.6 months?95%confidence interval[CI]9.8-11.3 months?,with 1-,3-,and 5-year survival rates of 43.7%,14.8%,and 8.8%,respectively.By Cox multivariate analysis,the following factors were identified as independent predictors of survival:gender?female vs male,hazard ratio 0.72,95%CI:0.54-0.95?,elevated total bilirubin?TBil;1.82,1.34-2.47?,elevated carbohydrate antigen 19-9?CA19-9;1.72,1.17-2.54?,being located in body and tail of pancreas?1.52,1.10-2,10?,advanced T stage?T3-4 vs T1-2:1.62,1.15-2.27?,lymph node metastasis?1.57,1.20-2.07?,distant metastasis?1.59,1.12-2.27?,receiving tumor resection?0.53,0.34-0.81?,and receiving systemic chemotherapy?0.62,0.45-0.82?.Neutrophil-to-lymphocyte ratio?NLR?,derived neutrophil-to-lymphocyte ratio?dNLR?,monocyte-to-lymphocyte ratio?MLR?,and platelet-to-lymphocyte ratio?PLR?were all independent prognostic factors of pancreatic cancer?NLR:HR 1.23,1.03-1.46;dNLR:HR 1.22,1.02-1.46;MLR:HR 1.63,1.27-2.09;PLR:HR 1.38,1.11-1.72?,which had obvious prognose evaluation value?P<0.05?.The prognose evaluation value of dNLR was significantly better than that of CA19-9?P = 0.048?,NLR had slight advantages?P = 0.054?,and the prognostic value of MLR and PLR were comparable to that of CA19-9?P>0.1?.Systemic Immune-Inflammation Index?SII?was not an independent influencing factor for the prognosis of pancreatic cancer?HR 1.09,0.92-1.29?,but lymphocyte-to-sum-of-monocyte-and-neutrophil ratio?LTMNR?was?HR 0.81,0.68-0.96?.LTMNR had a significant prognose evaluation value?P<0.05?and it was better than CA19-9?P<0.05?.None of Glasgow prognostic score?GPS?,modified Glasgow prognostic score?mGPS?,prognostic nutritional index?PNI?or C-reactive protein?CRP?to albumin ratio?CAR?was the indepent prognostic value of pancreatic cancer?P>0.05?.CRP to prealbumin ratio?CRP/pAlb?was an independent prognostic factor of pancreatic cancer?HR 1.43,1.05-1.95?,and it was better than CA19-9?P<0.05?.In conclusion,the prognosis of pancreatic cancer was poor,and most of patients was in advanced stages when they were diagnosed.There were several factors related to poor prognosis in patients of pancreatic cancer,including being male,elevated TBil and CA19-9,being located in the body and tail of pancreas,advanced T stage,lymph node metastasis,distant metastasis,absence of tumor resection,and absence of systemic chemotherapy.NLR,dNLR,MLR,PLR,LTMNR,and CRP/pAlb were all independent factors influencing the prognosis of pancreatic cancer,and all of them have significant prognose evaluation value.SII,GPS,mGPS,PNI,and CAR were not independent factors that influence the prognosis of pancreatic cancer.According to the research of limited cases in the single center,the prognostic value of dNLR,LTMNR,and CRP/pAlb significantly better than that of CA19-9,the prognostic value of NLR had slight advantage,while MLR and PLR were comparable to that of CA19-9.The prognosis of pancreatic cancer is poor.Lacking of markers for diagnosis and prognosis is one of the most important factors that affect the survival of patients with pancreatic cancer.Circular RNA?circRNA?is expected to be a new generation of clinical biomarkers for its stability and specificity of expression.The aim of this study is to screen out relatively highly expressed circRNAs in pancreatic cancer compared to healthy people or patients with chronic pancreatitis,and to further verify its value as a diagnostic and prognostic marker.In our study,we detected the circRNA sequencing within peripheral blood from pancreatic cancer patients,chronic pancreatitis patients,and healthy human by high-throughput circRNA sequencing.Then we conducted bioinformatics analysis for the detected circRNAs,including analyzing the length distribution,sources,genomic enrichment of the origin genes and expression differences,and screened out several highly expressed circRNAs in pancreatic cancer patients as candidate markers.These circRNAs were then screened out again in the training group;and we detected the diagnostic efficiency of the determined differentially expressed circRNA.Then the diagnostic value of the circRNA was assessed among the blinding validation group;the sensitivity,specificity,and accuracy of the diagnostic marker were also calculated.Kaplan-Meier,log-rank test,and Cox regression were used to determine the impact of the circRNA expression on the prognosis of pancreatic cancer.Through sequencing and bioinformatics analysis of peripheral blood in 3 cases of pancreatic cancer,2 cases of chronic pancreatitis,and 2 healthy controls,8 highly expressed circRNAs in peripheral blood of pancreatic cancer patients were selected as candidate diagnostic markers for pancreatic cancer.After the detection of these circRNAs in the training group?26 cases of pancreatic cancer patients,11 cases of chronic pancreatitis patients,and 20 cases of healthy controls?,only one circRNA?hsa_circ₀007564?was found to be highly expressed in peripheral blood of patients with pancreatic cancer,suggesting that hsa_circ₀007564 circRNA could be used as a marker for diagnosis of pancreatic cancer,with the sensitivity,specificity,and accuracy to distinguish between pancreatic cancer and non cancer being 69.2%,83.9%,and 77.2%,respectively.Further validation was carried out in the validation group?11 cases of pancreatic cancer,5 cases of chronic pancreatitis,9 cases of healthy controls?.Being used as a diagnostic marker,the sensitivity,specificity,and accuracy of hsa_circ₀007564 were 63.6%,85.7%,and 76.0%,respectively.Lastly,in prognostic analyses group?83 cases of pancreatic cancer?,by using multivariate analysis,adjusted by age,sex,smoking,drinking,body mass index,tumor location,tumor stage,and treatment modality,high hsa_circ₀007564 expression was an independent prognostic factor for poor survival,with the harzard ratio being 2.67?95%confidence interval[CI]1.72-8.33,P = 0.011?.Hsa_circ₀007564 is highly expressed in peripheral blood of patients with pancreatic cancer and can be used as a new diagnostic marker for the diagnosis of pancreatic cancer.In patients with pancreatic cancer,high expression of hsa_circ₀007564 is an independent impact factor of poor prognosis.