Integrative-analysis Of Long Non-coding RNA In Hepatocellular Carcinoma

Hepatocellular carcinoma is a global malignant cancer with a high mortality.The molecular mechanism in HCC invasion and progression is still unclear.Recently,several studies show that the dysregulation of long non-coding RNAs(lnc RNAs)plays a critical role in cancer cell development,and have been implicated to be potential biomarkers for cancer prognosis.However,the common prognostic lnc RNA signature in HCC remains uncertain.Moreover,the differences in lnc RNA expression between HCC stages are unclear as well as the biological function.Based on the high-throughput sequencing and the growing lnc RNA annotations,it is possible to explore the role of lnc RNA in HCC.In this study,by using public HCC transcriptome data and bioinformatics skills,we present the prognostic ability of lnc RNA in HCC overall survival and the impact of lnc RNA dysregulation in HCC development and the associated lnc RNA in HBV integration.First,we analysed the prognostic ablility of lnc RNAs in HCC.We chose two public HCC transcriptome datasets as the resource: one dataset contained 364 expression profiles of HCC patients from The Cancer Genome Atlas project(TCGA),which was divided into a training set and a test set;another public dataset as a validation set containing 221 expression profiles of HCC patients from GSE14520 in GEO database.Four lnc RNAs were identified to be significantly associated with the HCC overall survival in the training set.Based on the expression of these lnc RNAs,we produced a risk score(RS)model to distinguish the poor progonosis among HCC patients.The RS model showed its good prognostic capability in the test and validation set.Using the subgroups of HCC patients with different clinicopathological factors,the independence of the model was confirmed.Besides,Gene set enrichment analysis suggested that these lnc RNAs were involved in several liver cancer cell pathways.This work indicated that the RS model based on the lnc RNA signature could be a useful marker to determine the diagnosis and predict the prognosis of HCC.In order to investigate the dynamic changes and correlated functions of the lnc RNAs in HCC progression,TCGA HCC patients in different stages were chosen to analysis as they have PCG and lnc RNA expression information.Due to the different expression analysis,we identified DE-lnc RNAs and DE-PCGs in each stage.The co-expression relationship between DE-lnc RNA and DE-PCG became the base of constructing the stages specific lnc RNA-PCG network.By mining the similarity between lnc RNAs and PCGs profiles,six lnc RNA-PCG functional modules were presented.Among these modules,two modules are stage-specific.One is correlated with the early tumor stage and the other is found in the later stage in contrast.Clinical results showed that hepatitis B Virus(HBV)could integrate into human genome.HBV integration weakened the instability of the host genome and contributed to hepatocarcinogenesis.Many researches have revealed gene dysregulation after HBV integration.However,these papers tended to focus on coding gene rather than non-coding transcripts.Thus,we aimed to explore the lnc RNA dysfunctions in host genome integrated by HBV.By analysising 8 public HBV integration sequencing datasets,the distribution of HBV integration site showed that the lnc RNAs were potential target of the virus.In addition,based on the expression profiles from TCGA,271 different expressed lnc RNAs were identified to be integrated by HBV in the tumor samples.Basing on the annotation and enrichment analysis,we found that the integrated lnc RNAs associated protein coding genes contributed to viral invasion and were correlated with the HCC invasion.In recent years,more evidences showed the relationship between lncRNAs and diseases.Lnc RNA dysregulation was found in many diseases.Thus,data remining was useful to improve the knowledge about lnc RNA'roles in disease processing.Based on the existent resource,we collected more lnc RNA-disease dysregulation researches through searching pubmed by using proper keywords.After manual remining,we collected a huge number of lnc RNA-disease dysregulation results with proof methods.Afterwards the Lnc RNADisease database was updated.In the new database Lnc RNADisease v2.0,the associated species number was expended to 4.The sum of lnc RNA-disease dysregulation records increased from 2947 to 10032.Meanwhile,247 new circular RNA-disease records were added to the database.In addition,we introduced a method-based model to grade each lnc RNA-disease dysregulation.The new database also improved several interactive functions,such as search and browser.Users could find sorts of lnc RNA-disease dysregulation with no limit and submit new dysregulation records.In summary,we explored the lnc RNAs in HCC from several aspects.It was shown that the lnc RNAs played important roles in invasion,progmosis and HBV integration.It was possible to use the lnc RNAs in HCC prevention and cure.