| Pancreatic cancer is one of the malignant neoplasms with bad prognosis and high mortality,and the metastasis of tumor cells is the main cause of death of pancreatic cancer patients.The cells of pancreatic cancer which could break through basement membrane,penetrate into the bloodstream,and migrate to other tissues or organs with the circulatory system are called circulating tumor cells（CTCs）.Recent studies shown that CTCs captured in fluid biopsy have prognostic significance.Further more,there is growing evidence that studying of intrinsic molecular mechanism of the anoikis resistance,survival in fluid shear stress and dodge immune surveillance of CTCs,the potential seed that initiates distant metastases by shedding from the primary tumor,will provide new ideas for tumor treatment and metastasis interruption.However,the inherent mechanism of CTCs is still inadequate,and the key regulatory factors,different transcriptional patterns,the mechanisms of survival and immune escape,and the exact relationship between key genes of CTCs and the survival of the patients have not been systematically studied.To investigate the mechanisms of the genes in CTCs,we started this study by downloading the transcriptome data of 187 samples with 75 pancreatic cancer CTCs form GEO database,identifying novel lncRNA and find the key lncRNA which plays an important role in expression regulation by calculating the correlation of expression between gene-pairs and structuring co-expression networks.Based on the transcriptome with novel CTCs-specific lncRNA,we identified different expression patterns of pancreatic cancer CTCs and try to restore the tiering relationship between them.Mean while,preservation statistics for multiple cancer CTCs datasets was performed separately for revealing the universal expression pattern in CTCs.Furthermore,the survival-related genes in pancreatic cancer CTCs were calculated by survival analysis performed on the data obtained by combining the expression profiles and clinical data of genes in preserved module of pancreatic cancer patients in the TCGA and ICGC databases with CTCs genes.Finally,after being trained andtested in two tumor database,a prognostic-related survival models composed of multiple CTCs gene was obtained with excellent performance,which may further explained the importance of CTCs key genes in survival and prognosis.By performing a series of analysis,we identified 2026 novel lncRNA with high confidence in pancreatic cancer CTCs,obtained a robust result of CTCs subtypes,recovered the relationship between CTCs subtypes,identified the key signal pathways such as Wnt signal pathways and several lncRNA,such as XLOC054311,XLOC007054,XLOC082573,as key regulators and hub-genes of co-expression networks in pancreatic cancer CTCs.In verification analysis of expression pattern of CTCs,we identified 3 modules as preserved gene expression patterns in CTCs in multiple cancer types,and these results may have important sense for the studying of common survival molecular mechanism of CTCs from different sources.By combining the genes expression with clinical data of patients in2 tumor databases,we obtained preserved gene expression patterns including 76 genes and a survival model consist of 5 genes（ANKRA2,GBP2,KRT19,DOCK9,TRIM46）with excellent performance in training and testing sets,and found the XLOC011657,which is the hub novel lncRNA in CTCs co-expression network,may regulate expression of target gene KRT19,which plays an important role in pancreas cancer,and may be a potential targeted therapeutic genes.All these findings will undoubtedly be used as guidance for targeted therapy,tumor metastasis blocking and further studying of intrinsic mechanism of CTCs. |
