| Part 1 Transcription factor SLA2 regulated genes predict the survival of breast cancer patientsPurpose:This study is to identify the molecules associated with the survival of breast cancer patients.Method:Gene expression and clinical information was obtained from GSE62944 with 1119 breast cancer samples and 113 normal samples.Cox scores were calculated with supervised principal components and the correlation between gene expression and patient survival was studied.The top 25 genes with max Cox scores were selected for patient classification,and the patients were classified into 4 subgroups by ConsensusCluster.And 12019 differentially expressed genes and co-expression analysis was performed to found modules changed among the subgroups.Transcription factor(TF)regulation network was constructed so as to discover the key TFs associated with cancer survival.Results:The samples were divided 4 subgroups by 25 genes with the max Cox scores and survival curve of the 4 subgroups was significantly different,however,functional enrichment analysis showed no meaningful results for the 25 genes.Subgroups 1,2,and 4 were chosen to screen molecular mechanisms underlying the different survival curve.Then a co-expression module,which contained genes that involved in adaptive immune response,was found to associate with the survival difference among the three subgroups.In addition,the genes in the module were regulated by TF SLAP2 and could predict the outcome of breast cancer more robustness and sensitivity.Conclusion:Genes involved in adaptive immune response regulated by TF SLAP2 are associated with the survival of breast cancer patients.Part 2 SLAP2 regulates the malignant development of breast cancer by inhibiting the mTOR pathwayPurpose:In recent years,breast cancer treatment technology have been greatly improved and progress.The majority of breast cancer patients who are treated by surgery,radiotherapy,chemotherapy,endocrine therapy and molecular target can be greatly improved.However,there are still many breast cancer patients who suffer from tumor recurrence and metastasis.Actively seeking new treatments for breast cancer and overcoming cancer resistance have become the focus of current breast cancer treatment.SLAP proteins are a class of proteins expressed in various types of cells,but are the most extensively studied in lymphocytes.In recent years,studies have shown that SLAP2 is also involved in the occurrence and development of tumors.However,there have been no studies on whether SLAP2 is involved in breast cancer development.Methods:First,we detected the mRNA and protein levels of SLAP2 in breast cancer tissues compared with that of normal controls using real time PCR and Western blot.At the same time,the expression of SLAP2 was detected in MDA-MB-231 cells in vitro,and its effects on malignant proliferation,migration,invasion and apoptosis of tumor cells were detected.In addition,we analyzed the effect of abnormal expression of SLAP2 on activation of mTOR signaling pathway.Results:Iin this study,we first explored the expression of SLAP2 in breast cancer and found that the SLAP2 and protein levels of mRNA were significantly lower in breast cancer samples.Further research found that the decreased expression of SLAP2 in breast cancer cells,can significantly promote the activation of mTOR signaling pathway,thereby causing breast cancer cells malignant proliferation,migration and invasion,and reducing the level of apoptosis of breast cancer cells.In contrast,overexpression of SLAP2 in breast cancer cells can significantly inhibit the activation of the mTOR pathway,decrease the proliferation,migration and invasion of MDA-MB-231 cells,and induce apoptosis in breast cancer cells.Conclusion:SLAP2 is an anti tumor factor in course of the development and progression of breast cancer.It inhibits the malignant development of breast cancer by inhibiting the activation of mTOR signaling pathway.These results suggest that SLAP2 may be a potential target for future breast cancer treatment. |
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