The Initial Research Of Long Noncoding RNA Which Related To Liver Depression Syndrome Of Preoperative Breast Cancer

[BACKGROUND]Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer death among women. LncRNA (Long non-coding RNA, lncRNA) are functional RNAs longer than 200 nucleotides in length. Growing evidence suggests that lncRNAs are key regulators which governing various biological processes such as genomic imprinting, transcription activation and inhibition, chromatin modification and tissue development. Dysregulation of lncRNAs have performed critical roles in many human diseases, including various types of cancers.In the theory of traditional Chinese medicine (TCM), etiology and pathogenesis of BC have long been recognized. On these basic theories, TCM physicians have developed their typical opinions on BC diagnose and treatment. Liver depression has been considered as the key point and the main syndrome type in BC syndrome differentiation. It also showed the importance of liver depression syndrome in breast cancer and provided ideas for clinical strategy. With the development of modern science, several experimental and clinical studies have found that liver depression syndrome is closely related to BC. More recently, numerous lncRNAs have been shown to exert oncogenic or tumor suppressor properties in BC. However the potential roles that lncRNAs regulate breast cancer with liver depression syndrome are still poorly understood. Further study on liver depression syndrome in BC procession may not only helpful to TCM syndrome related study but also to screen high-risk BC groups and improve the early diagnosis rate and may find new drug targets.[AIMS]To investigate the expression profile of lncRNA in the BC combined liver depression syndrome. Screen liver depression syndrome BC related lncRNAs. Study on such lncRNAs potential rules in the procession of liver depression syndrome procession. Assess the clinic value of liver depression syndrome BC related lncRNAs[METHODS]IN FIRST STEP. We constructed BC related lncRNA libraries by using Microarray. Quantitative real-time reverse transcription PCR (qRT-PCR) were used to test and verify the microarray data in 22 paired tissues. GO analysis and pathway analysis were performed to determine the gene and gene product enrichment.IN SECOND STEP. We measured circulating serum lncRNA RP11-445H22.4 expression levels in 68 BC combined liver depression syndrome patients and 68 healthy donors. Receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic values of lncRNA RP11-445H22.4. Also the potential correlations between circulating lncRNA RP11-445H22.4 expression levels and patient clinicopathological factors are further investigated.[RESULTS]Microarray expression profiling suggests 790 up-regulated and 637 down-regulated (log fold-change>2.3), lncRNAs were differently expressed between liver depression syndrome BC tissues and its paired adjacent tissues. The qRT-PCR results and microarray data are consistent. We found that most biological process of up regulated lncRNAs are involved in immune regulation and biological process of down regulated lncRNA are enriched in development process. Pathway analysis indicated that 44 pathways corresponded to under-regulated transcripts and 31 pathways corresponded to up-regulated transcripts.Down-regulated lncRNAs enriched involved in a category "Calcium signaling" has been reported involved in the development of BC. Most of the pathways that up-regulated lncRNA enriched are also related with immune system.Furthermore, we foundRP4-583P15.10, an up-regulated lncRNA, was found to be located downstream of the natural antisense of the ZBTB46 gene, which may regulated breast cancer through influence immune system. An under-regulated lncRNA RP11-445H22.4 was found to be located downstream of the intron of the WNT1-inducible signaling pathway protein 2 (WISP2), may associated with the progression of breast cancer.In BC combined liver depression syndrome patients, the expression level of lncRNA RP11-445H22.4 is significantly increased (p<0.001). The sensitivity and specificity of RP11-445H22.4 for diagnose were 92% and 74% respectively. Compared the sensitivity and specificity in scanning BC by ultrasound and lncRNA RP11-445H22.4.The specificity in lncRNARP11-445H22.4 and ultrasound was nearly, but lncRNA RP11-445H22.4 had better sensitivity. The expression levels of lncRNARP11-445H22.4 was correlated with ER, PR and menopausal status of the breast cancer patients (p<0.05).[CONCLUSION]LncRNAs palyed an important role in the development of BC combined liver depression syndrome may by regulating immune system.For the detection of BC combined liver depression syndrome patients, the use of RP11-445H22.4 showed a remarkable improvement compared with the clinical serum carcinoembryonic antigen. lncRNA RP11-445H22.4 may be a new potential biomarker of breast cancer.