Expression Levels Of Long-noncoding RNA CCAT2 And LSINCT5 In Breast Cancer Serum And Bioinformatical Analysis

Objective: To assess the expression of lncRNA-CCAT2 and lncRNA-LSINCT5 and their clinical value in breast cancer(BC)serum specimens.Bioinformatics methods were used to predict and analyze the target genes of CCAT2 and LSINCT5,and further to explore the potential functions,pathways and hub genes of their target genes.Methods: Serum specimens from 90 breast cancer patients,88 breast benign disease patients and 94 healthy controls were collected.The expression levels of serum CCAT2 and LSINCT5 were tested by qRT-PCR and relationship between their expression and clinical characteristics were analyzed.The expression levels serum CA15-3 and CEA in BC patients who were divided into I stage and II stage based on TNM and normal controls were tested by electrochemiluminescencewitch.Receiver operating characteristic(ROC)curve was performed to evaluate the diagnostic values of single index and combined indexes.Besides,35 pairs pre-operation and post-operation serum samples were detected by qRT-PCR to assess the tumor monitoring values.The target genes of CCAT2 and LSINCT5 were predicted.Meanwhile,GO annotation,KEGG analyses,PPI network and screen of target gene were performed.Results: the expressions of CCAT2 and LSINCT5 were increased in BC serum.Results of clinical characteristics analyses showed that: serum CCAT2 levels were correlated with estrogen TNM stage,lymphnode metastasis and PR(P<0.05),while they were uncorrelated with age,pathological pattern,ER,Her2 and Ki-67(P>0.05);serum LINCT5 levels were correlated with estrogen TNM stage,lymph node metastasis,PR and Ki-67(P<0.05),while they were uncorrelated with age,pathological pattern,ER and Her2(P>0.05).Compared with the healthy individuals,the diagnostic value of CCAT2(AUC=0.78,sensitivity=0.632,specificity=0.882,P<0.01)was significantly bigger than LSINCT5,CA15-3 and CEA when diagnosis by single index.Meanwhile,diagnostic value of combining 4indexes(AUC=0.83,sensitivity=0.691,specificity=0.927)were the biggest when diagnosis by multiple indexes.Compared with the breast benign disease patients,the diagnostic value of CCAT2(AUC=0.77,sensitivity=0.588,specificity=0.912,P<0.01)was significantly bigger than LSINCT5 Furthermore,serum CCAT2(P= 0.002)and LSINCT5(P= 0.005)levels were significantly decreased in postoperative samples than preoperative samples.The 26 target genes of CCAT2 and 40 target genes of LSINCT5 were identified by multiple methods.Enrichment analysis results showed that the target genes of CCAT2 were mainly enriched in mRNA processing,RNA splicing,regulation of transcription,cytoplasmic stress granule,RNA binding,poly(A)RNA binding and MicroRNAs in cancer,while the target genes of CCAT2 were mainly enriched in mRNA processing,RNA splicing,cytoplasmic stress granule,mRNA binding,nucleoplasm,poly(A)RNA binding,mTOR signaling pathway and AMPK signaling pathway.Moreover,SRSF1,SRSF9 and ELAVL1 were identified as the top3 hub genes from proteins interactive network between target genes ofCCAT2.Meanwhile,SRSF1,SRSF9 and PTBP1 were identified as the top 3hub genes from proteins interactive network between target genes of LSINCT5.Conclusion: CCAT2 and LSINCT5 both were overexpressing in BC serum and may serve as new biomarkers for BC diagnosis and prognosis monitor.The target genes of CCAT2 and LSINCT5 participated in lots of biological process and played a vital role in tumorigenesis and development of BC,which may improve our understanding of the molecular mechanisms underlying BC progression.Besides,key target genes may have some relationship with lncRNAs,and may provide new targets and directions for further exploring lncRNAs in BC.