RESUMO
One of actively developing trends in modern pharmacology is the use of the transcriptome analysis for drug repositioning. We have previously detected two molecular markers of relapses in patients with malignant breast tumors: ELOVL5 and IGFBP6. Poor prognosis is associated with low expression of these markers. Here we analyze the effects of simvastatin and a new potential proteasome inhibitor K7174 inducing expression of IGFBP6 and EVOVL5 on the proliferation of breast cancer cells MDA-MB-231 and DU4475. Compound K7174 potentiates the inhibitory effect of simvastatin on the proliferation of DU4475 cells characterized by low expression of ELOVL5-IGFBP6 pair, but not on the proliferation of MDA-MB-231 cells with high expression of these markers.
Assuntos
Neoplasias da Mama/microbiologia , Acetiltransferases/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Combinação de Medicamentos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Elongases de Ácidos Graxos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Recidiva Local de Neoplasia , Sinvastatina/farmacologia , Transcriptoma/efeitos dos fármacos , Transcriptoma/genéticaRESUMO
Profiles of circulating microRNA in the plasma of patients with prostate cancer with pathomorphological stages pT2, pT3, and pT4 are analyzed. The level of circulating microRNA hsa-miR-619-5p is elevated in patients with extracapsular spreading of the tumor, increasing significantly from stage pT2 to stage pT4.
Assuntos
Biomarcadores Tumorais/sangue , MicroRNAs/genética , Neoplasias da Próstata/sangue , Cisplatino/farmacologia , Docetaxel , Granulócitos/efeitos dos fármacos , Granulócitos/metabolismo , Humanos , Masculino , MicroRNAs/sangue , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Taxoides/farmacologiaRESUMO
We performed diagnostic classification of plasma specimens from patients with non-metastatic and metastatic prostate cancer based on pairs of miRNA that have no individual diagnostic significance. Of 230 miRNA detected in plasma specimens, 3 pairs were diagnostically significant. The miRNA pair hsa-miR-19b-3p and hsa-miR-297 demonstrated highest sensitivity and specificity. Among common target genes of these miRNA, CFL2 gene associated with cell mobility was detected.
Assuntos
Biomarcadores Tumorais/genética , Cofilina 2/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias da Próstata/diagnóstico , Idoso , Biomarcadores Tumorais/sangue , Cofilina 2/sangue , Humanos , Calicreínas/sangue , Calicreínas/genética , Metástase Linfática , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Gradação de Tumores , Antígeno Prostático Específico/sangue , Antígeno Prostático Específico/genética , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Sensibilidade e Especificidade , Transdução de SinaisRESUMO
Genes with significant differential expression are traditionally used to reveal the genetic background underlying phenotypic differences between cancer cells. We hypothesized that informative marker sets can be obtained by combining genes with a relatively low degree of individual differential expression. We developed a method for construction of highly informative gene combinations aimed at the maximization of the cumulative informative power and identified sets of 2-5 genes efficiently predicting recurrence for ER-positive breast cancer patients. The gene combinations constructed on the basis of microarray data were successfully applied to data acquired by RNA-seq. The developed method provides the basis for the generation of highly efficient prognostic and predictive gene signatures for cancer and other diseases. The identified gene sets can potentially reveal novel essential segments of gene interaction networks and pathways implied in cancer progression.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/genética , Transcriptoma , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Proteínas de Neoplasias/metabolismo , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismoRESUMO
The search for novel parameters to predict the risk of relapse in breast cancer was conducted. Significant correlation between the risk of relapse and α-2A adrenergic receptor (ADRA2A) expression was revealed using public microarray datasets. This relationship was confirmed by validation on independent microarray dataset. It was found that when assessing the risk of BC relapse, the accuracy of prediction based solely on the expression of ADRA2A gene is close to that made using OncotypeDX and MammaPrint test systems. In this case, addition of only one or two supplemental prognostic markers (for instance, expression of SQLE gene or SQLE and DSCC1genes) to ADRA2A ensures the accuracy of prediction not inferior to reliability of these test systems.
Assuntos
Algoritmos , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Recidiva Local de Neoplasia/genética , Receptores Adrenérgicos alfa 2/genética , Neoplasias da Mama/diagnóstico , Proteínas de Transporte/genética , Bases de Dados Genéticas , Feminino , Expressão Gênica , Humanos , Metionina Sulfóxido Redutases/genética , Recidiva Local de Neoplasia/diagnóstico , Estadiamento de Neoplasias , Proteínas Nucleares/genética , Valor Preditivo dos Testes , Prognóstico , Risco , Esqualeno Mono-Oxigenase/genética , Análise Serial de TecidosRESUMO
The paper presents a formalized statement of the problem of selecting parameters and construction of a genomic classifier for medical test systems with mathematical methods of machine learning without the use of biological and medical knowledge. A method is proposed to solve this problem. The results of testing the method using microarray datasets containing information on genome-wide transcriptome of the samples of estrogen positive breast tumors are discussed. Testing showed that the quality of classification provided by the constructed test system and implemented on the basis of assessments of expression of 12 genes is not inferior to the quality of classification carried out by such test systems as OncotypeDX and MammaPrint.
Assuntos
Neoplasias da Mama/diagnóstico , Software , Neoplasias da Mama/classificação , Neoplasias da Mama/metabolismo , Feminino , Perfilação da Expressão Gênica , Genômica , Humanos , Receptores de Estrogênio/metabolismo , Máquina de Vetores de SuporteRESUMO
We compared the results of real-time PCR analysis of gene expression in paired specimens breast cancer tissue fixed in RNAlater (Qiagen) stabilization reagent (FF samples) and in formalin (FFPE samples). A clear-cut linear relationship (correlation coefficient 0.76 ± 0.07) was detected between the gene expression logarithm values in FF and FFPE samples. This fact suggests that collections of paraffin blocks with formalin-fixed tissue specimens from patients with a many-year disease history can be effectively used in modern studies.
Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Perfilação da Expressão Gênica/métodos , Fixação de Tecidos/métodos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Feminino , Fixadores/química , Formaldeído/química , Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estabilidade de RNA , Kit de Reagentes para DiagnósticoRESUMO
We analyzed the expression of transcription factor c-Fos induced by neural activity in the mouse brain after acoustic stimulation. The brain sections of the animals subjected to acoustic stimulation and controls were immunohistochemically stained for c-Fos protein. Statistical parametric mapping (SPM) was used to identify group differences in the acquired images. c-Fos expression was significantly higher in the auditory cortex, amygdala, and hippocampus CA3 area after tone presentation. The proposed combination of SPM with molecular-biological approach to visualization of transcription in the nerve cells makes it possible to identify the collaborative activation of distant brain structures assumed to be the components of united functional systems.
