The extracellular secretion of miR-1825 wrapped by exosomes increases CLEC5A expression:A potential oncogenic mechanism in ovarian cancer

Background:Ovarian cancer(OC)is a leading cause of gynecological cancer-linked deaths worldwide.Exosomal miR-1825 and its target gene C-type lectin domain family 5 member A(CLEC5A)are associated with tumorigenesis in cancers that was further probed.Methods:Exosomal miR-1825 expression in exosomes and its impact on overall survival(OS)prediction were determined using Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)data.Target genes of miR-1825 were searched in five prediction databases and prognostically significant differentially expressed genes were identified.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were carried out.The ability of CLEC5A to predict OS was evaluated using univariate and multivariate Cox regression analyses and Kaplan-Meier curves.The CLEC5A expression pattern in OC was validated using immunohistochemistry.The CIBERSORT algorithm was used to compare the immune cell landscape,and the results were validated in a GEO cohort.Finally,the predicted half maximal inhibitory concentration(IC50)values for five commonly used chemotherapy agents were also compared.Results:MiR-1825 level was higher in exosomes derived from OC cells and served as a tumor suppressor.The CLEC5A gene was found to be a target of miR-1825,the upregulation of which was correlated with a poor prognosis.M2 macrophage infiltration was significantly enhanced in the CLEC5A high expression group,while T follicular helper cell infiltration was reduced in it.While the predicted IC50 for cisplatin and doxorubicin was higher in the CLEC5A high expression group,that of docetaxel,gemcitabine,and paclitaxel was lower.Conclusion:MiR-1825,a promising OC biomarker,may promote OC progression by increasing CLEC5A expression via exosome-mediated efflux from tumor cells.

Multi-omics joint analysis revealed the metabolic profile of retroperitoneal liposarcoma

Retroperitoneal liposarcoma(RLPS)is the main subtype of retroperitoneal soft sarcoma(RSTS)and has a poor prognosis and few treatment options,except for surgery.The proteomic and metabolic profiles of RLPS have remained unclear.The aim of our study was to reveal the metabolic profile of RLPS.Here,we performed proteomic analysis(n=10),metabolomic analysis(n=51),and lipidomic analysis(n=50)of retroperitoneal dedifferentiated liposarcoma(RDDLPS)and retroperitoneal well-differentiated liposarcoma(RWDLPS)tissue and paired adjacent adipose tissue obtained during surgery.Data analysis mainly revealed that glycolysis,purine metabolism,pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue,whereas the tricarboxylic acid(TCA)cycle,lipid absorption and synthesis,fatty acid degradation and biosynthesis,as well as glycine,serine,and threonine metabolism were downregulated.Of particular importance,the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway(PPP)inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor abemaciclib.Our study not only describes the metabolic profiles of RDDLPS and RWDLPS,but also offers potential therapeutic targets and strategies for RLPS.

原发性乳腺癌患者治疗前血清TPS水平与预后之间的关系(英文)

Objective: The aim of this study was to explore the correlation of pretreatment serum tissue polypeptide specific antigen (TPS) with prognosis in primary breast cancer. Methods: A total of 361 patients with grades I-III breast cancer had been followed up from January 2001 to February 2011. Serumal TPS level was measured by enzyme-linked immunosorbent assays (ELISA). Univariate and multivariate analyses were used to investigate associations between pretreatment TPS level and clinicopathological parameters and patient outcomes. Results: First, at the univariate analysis, the expression of TPS was related with some clinicopathological traditional prognostic factors such as tumor size (P = 0.030), histologic grade (P = 0.001) and lymph node status (P = 0.008). Second, overall survival were significantly shorter among patients with elevated pretreatment serum TPS (P = 0.038). However, finally, multivariate Cox regression indicated that the level of pretreatment serum TPS was not an independent prognostic parameter for overall survival in primarily breast cancer patients (P > 0.05). Conclusion: The expression of pretreatment serum TPS is closely correlated with clinicopathology parameters and overall survival of patients with primarily breast cancer, but its level has no independent prognostic value.