Expression And Clinical Significance Of Long Non-coding RNA RP11-466I1.1 In Hepatocellular Carcinoma

Background and Aims:Hepatocellular carcinoma(HCC),accounting for 70%-90%of primary liver cancer,is the predominant pathological type,whose insidious onset,high malignant degree,strong invasive ability and poor prognosis make it one of the most common leading cause of cancer-related death worldwide.Both insufficiency of early diagnosis and treatment and lack of effective therapeutic method in advanced stage are responsible for the high mortality of HCC.It is crucial for improving the prognosis of HCC to explore the molecular mechanisms during HCC pathogenesis and to find accurate and reliable biomarkers for early diagnosis and prognosis accordingly.The occurrence and progression of tumors is a complicated pathological process with the participation of multi-factors and multi-mechanisms.Recently,lipid metabolism deregulation has been considered as one of the important factors associated with cancer pathogenesis.Long noncoding RNAs(IncRNAs),a class of non-coding transcripts with the length of more than 200 nucleotides,have been recognized as functional fragments in many biological processes,including the regulation of lipid metabolism.Lots of studies showed that,on one hand,several IncRNAs participate in lipid metabolism regulation;on the other hand,the dysregulation of lncRNAs expression play important roles in HCC pathogenesis though regulating cell proliferation,differentiation and apoptosis.In the present study,we focus on long non-coding RNA RP11-466I1.1,which was firstly identified as an upregulated IncRNA in response to lipopolysaccharide(LPS)stimulation in human umbilical vein endothelial cells(HUVECs)by Singh,K.K.et al,It is the only one publication involving this lncRNA and it is still unknown whether it plays roles in tumors.Before the present study,we have found the differential expression of RP11-46611.1 in HCC.Therefore,we continued to studying its expression and clinical significance in HCC.In this study,we aimed to detect the expression levels of RP11-46611.1 in human HCC,observe its correlations with clinical features,then analyze the effects of RP11-46611.1 on the cellular biological behaviors accordingly and further analyze its diagnostic and prognostic value in HCC.We also predict the target gene of RP11-466I1.1 by which it playing roles in HCC.Material and Methods:72 HBV-related HCC patients and 11 hepatic hemangioma patients were included.Expression levels of RP11-466I1.1 were detected by RT-PCR in tissue and serum level,and expression differences were analyzed by one-way ANOVA together with Dunnett-t test or independent 2-tailed t test.Clinical features were obtained and their correlations with RP11-466I1.1 were analyzed.Receiver operating characteristic(ROC)curve was performed to assess the diagnostic value of RP11-466I1.1 in serum.Kaplan-Meier method and Log-Rank test was used to evaluate the prognostic value of RP11-46611.1.At last,bioinformatic analysis was carried to predict the target gene of RP11-466I1.1.Results:RP11-466I1.1 was upregulated in HCC tissues(p<0.01)and serum(p<0.05).The expression level of RP 11-46611.1 was significantly correlated with two clinical features,histological grade and tumor capsule,while no significant correlation was found with other clinical features including age,sex,tumor size,cirrhosis,metastasis,AFP,CEA,and y-GT.Significant upregulation of RP11-46611.1 in HCC tissues with poorer histological grade(p<0.01)and incomplete tumor capsule(p<0.01)was found compared to that with better histological grade and complete tumor capsule,respectively.The diagnostic value of RP11-466I1.1 was not supported by ROC curve analysis(AUC=0.665,p=0.079).Yet the significant correlation of RP11-46611.1 with poor prognosis indicated its potential prognostic value in HCC.Bioinformatic analysis showed that RP 11-46611.1 might play roles in HCC pathogenesis by targeting LPL and PPAR-y.Conclusion:RP11-46611.1 is upregulated in HCC tissue and is significantly associated with the histological grade and tumor capsule integrity.RP 11-46611,1 is stably expressed and is upregulated in HCC.The expression level of RP11-466I1.1 in serum cannot serve as an effective diagnostic biomarker but may serve as a promising novel prognostic biomarker in HCC because of its correlation with the poor prognosis.Further bioinformatic analysis revealed the potential target gene LPL and PPAR-?,and it's highly possible that RP 11-46611.1 particpates in HCC pathogenesis through regulating lipid metabolism by targeting LPL and PPAR-y.