1 The Molecular Mechanism Of Wnt/?-catenin Pathway Interacting Long Noncoding RNA In Triple-Negative Breast Cancer Malignant Progression 2 Clinical Significance Of The B7-H4 As A Novel Prognostic Marker In Breast Cancer

PART I: THE MOLECULAR MECHANISM OF WNT/?-CATENIN PATHWAY INTERACTING LONG NONCODING RNA IN TRIPLE-NEGATIVE BREAST CANCER MALIGNANT PROGRESSIONObjective: To search Wnt/?-catenin pathway interacting long non-coding RNA in triple-negative breast cancer,and explore the molecular mechanism between long non-coding RNA and Wnt/?-catenin pathway,and investigate the clinical significance of long non-coding RNA in triple-negative breast cancer progression.Methods: We detect the RNA after transient flag-?-catenin plasmid in MDA-MB-231 by RIP-sequence.We select Wnt/?-catenin pathway interacting long non-coding RNA by above two ways.We detect theexpression,location and length by qRT-PCR,FISH,nuclear plasma separation,and 3??5? RACE assay.We explore the molecular mechanism among them by Western-blot,FISH,IF,RNA pull-down and protenin IP assay.We detect the lncRNA expression in tissues samples by RNA ISH,qRT-PCR assay,and value the relationship between lncRNA and overall survival by Kaplan-Meier plot.Results: LncRNA CTC-444N24.11 was closely associated with Wnt/?-catenin pathway by RIP-seq.The length is about 4600 bp,mainly located in cytoplasmic,it is negatively correlated with OS of triple-negative breast cancer patients.It can activate Wnt/?-catenin pathway by inhibiting?-catenin phosphorylation and then translocating into nuclear,there is a positive feedback between CCTC-444N24.11 and Wnt/?-catenin pathway.Conclusion: Long non-coding RNA CTC-444N24.11 ptomoted malignant processes by activating Wnt/?-catenin pathway in triple-negative pathway.CTC-444N24.11 was demonstrated to be an independent prognostic factor for triple-negative breast cancer patient outcomes.PART II CLINICAL SIGNIFICANCE OF THE B7-H4 AS A NOVEL PROGNOSTIC MARKER IN BREAST CANCERObjective: To explore the relationship between B7-H4 expression and breast cancer patients overall survival prognostic.Methods: We detected B7-H4 expression in breast cancer tissue samples using immunohistochemistry SP-2000,we analyzed the prognostic data using SPSS 19.0 and Kaplan-Meier,analyzed the relationship between B7-H4 expression and breast cancer clinical pathological features by GraphPad Prism 5.0.Results: We found that different expression levels of B7-H4 on breast cancer cells were significantly correlated with patients ? pTNM,overall survival,p53.Furthermore,univariate analyses showed that the overall survival rate of the patients with higher B7-H4 expression was significantly worse than of the patients with lower B7-H4 expression.Multivariate analyses showed that B7-H4 was a significant independent prognostic indicator.Conclusion: Our results suggest that B7-H4 might be closely associated with breast cancer progression.Its high expression may serve as a potential prognostic biomarker in human breast cancer.