PTHrP and SPARC expressions in human colorectal cancer: An in silico analysis

PTHrP is a paraneoplastic factor involved in the progression and theacquisition of the aggressive behavior of different types of tumors. Employing in vitroand in vivo models of colorectal cancer (CRC), our research group observed thatPTHrP promotes cell survival, proliferation, migration, angiogenesis, epithelial tomesenchymal transition (EMT) program, cancer stem cell (CSC) phenotype, andchemoresistance through different signaling pathways. Recently, in HCT116 cellsderived from CRC we found that PTHrP acts increasing SPARC protein expression, arelevant protein involved in CRC progression. Moreover, SPARC treatment on HCT116cells potentiated PTHrP effects. In vivo model, PTHrP also increased SPARC expression. Based on these findings, the aim of this work is explore the clinical relevance ofPTHrP and SPARC tumor expression in human CRC using in silico analysis.Methods: Cytoscape 3.8.2 stringApp was employed to visualize molecular networksfrom the STRING database related to CRC, and proteins associated with prognosticfactors were selected to analysis. Using STRING Enrichment App, the proteins networks (PN) merged were compared to establish enrichment. Finally, in silico tool andonline data sets (GEPIA2 and STRING 11.0) were used to explore the association ofPTHrP and SPARC and their prognostic value in 362 CRC human samples.Results: In GEPIA2 database, a significant correlation between the expressions ofPTHrP and SPARC in CRC was observed (p-value¼0.01). Also, SPARC expression washigher in CRC respect to colorectal normal samples (p-value¼0.01). In the same way,SPARC expression was significantly higher in CRC advanced than in early disease.Employing STRING 11.0 database, we observed a strong association between PTHrPand several oncogenic markers (CDH2, CD44, VIM, among others) that previouslywere evaluated in vitro by us linked through SPARC with a Protein-Protein interactionenrichment (p-value 0.95). This PN was merged with the PN obtained from the search?colorectal cancer? with a high disease score (SD> 3.2). From this analysis, VEGFA wasemerged as a central nexus between PTHrP and SPARC proteins. Finally, GEPIA2 wasused to evaluate the survival rate in CRC patients that express PTHrP and/or SPARC.No significant impact in overall survival was found taken account high or lowexpression of each protein.Conclusions: In CRC tumor samples, a strong relationship between PTHrP and SPARCexpression was found, suggesting that both proteins could be involved in the progression of the disease. Despite VEGFA was also associated with PTHrP/SPARC, morestudies are necessary to evaluate their clinical relevancy.Fil: Carriere, Pedro Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Novoa Díaz, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: López Moncada, Fernanda. Universidad de Chile. Facultad de Medicina.; ChileFil: Zwenger, A.. Centro de Estudios Clinicos SAGA; ChileFil: Contreras, H.. Universidad de Chile. Facultad de Medicina.; ChileFil: Calvo, Natalia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Gentili, Claudia Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaESMO World Congress on Gastrointestinal Cancer 2021Modalidad virtualEstados UnidosEuropean Society for Medical Oncolog

Metástasis cutáneas de cáncer de mama

El objetivo de este estudio es identificar perfiles correspondientes a la metástasis cutánea en el cáncer de mama mediante el análisis de marcadores tumorales tales como MUC1 y antígenos carbohidratos asociados

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment