Structural Variation Spectrum Of Pancreatic Cancer And Its Carcinogenesis/the Study Of The Prognostic Value Of LTMNR In Pancreatic Cancer

Structural variation spectrum of pancreatic cancer and its carcinogenesisBackground:Structural variations(SVs)are the greatest source of variation in the genome and can lead to oncogenesis.However,the identification and interpretation of SVs in human pancreatic cancer remain largely undefined due to technological limitations.Methods:The signatures of SVs in pancreatic cancer cell were first investigated by longread single-molecule real-time(SMRT)sequencing technology and the pathogenetic SVs that directly affect cancer-related genes in human pancreatic cancer were identified.Transcription profile were characterized using transcriptome sequencing techniques.Enhancer activity,expressional level and clinical prognosis datasets were acquired from public databases to validate above regulatory correlation or biological significance.Results:The global structural variation spectrum in human pancreatic cancer were first revealed.Meanwhile,the 3D chromatin architecture was also depicted and undergone widespread remodeling accompanied with gene expressional changes.The distributions of SVs among 3D genome architectures presented a strong cell type specificity.The study identified and further explored the impacts of cross-boundary SVs and found that the bulk remodeling effect observed in the 3D genome partly depends on intercellular genomic heterogeneity resulting from discrepancy of SV frequency.Moreover,the data also demonstrated complex genomic rearrangements involved in key driver genes CDKN2A,and elucidated its influence on cancer-related gene expression from both linear view and 3D perspective.Conclusion:Overall,this study highlights the impact,complexity and dynamicity of the interplay between SVs and 3D genome organization and further expands our understanding of pathogenesis of SVs in human pancreatic cancer.Prognostic Value of Pretreatment Lymphocyte-to-sum-of-monocyte-andneutrophil Ratio in Pancreatic Cancer is Higher than that of Carbohydrate Antigen 19-9:A Single-center Retrospective Analysis of 1433 Patients in ChinaBackground:There were growing evidences showed that systemic inflammatory response is associated with cancer prognosis.We aimed to compare the predictive value of lymphocyte-to-sum-of-monocyte-and-neutrophil ratio(LTMNR)and carbohydrate antigen 19-9(CA19-9)among patients with pancreatic cancer.Methods:Pretreatment LTMNR was retrospectively analyzed in pancreatic cancer patients.Predictive values of LTMNR and CA19-9 compared using univariable logistic regression models and time dependent receiver-operating characteristic(ROC)curve.Results:In 1,433 patients,the median overall survival(OS)was 10.6 months(95%confidence interval[CI]:9.8-11.3 months),with 5-year OS rates of 8.8%.At selected cut-point 10.6 months,the optimal cut-point for predictive value of LTMNR occurs at 0.31(RR=1.35,p<.0001)in X-tile plot analysis.The pancreatic cancer patients with higher LTMNR had lower CA19-9 and early stage tumors compared to those with lower LTMNR.Higher LTMNR value maintained a significant association with good prognosis(0.81[95%CI:0.68-0.96],p=0.015)in pancreatic cancer patients.The prognostic prediction model using LTMNR can improve the accuracy of prognosis evaluation about 4.6%compared to CA19-9.Predictive value of LTMNR is significantly higher than that of CA19-9(area under the curve[ΔAUC]:0.04[0.00-0.09],p=0.049).Higher LTMNR value significantly associated with better survival in patients with pancreatic cancer.Conclusion:Predictive value of LTMNR in pancreatic cancer is higher than that of CA19-9.