RESUMO
BACKGROUND: We analysed critically the potential usefulness of RNA- and DNA-based biomarkers in supporting conventional histological diagnostic tests for prostate carcinoma (PCa) detection. METHODS: Microarray profiling of gene expression and DNA methylation was performed on 16 benign prostatic hyperplasia (BPH) and 32 cancerous and non-cancerous prostate samples extracted by radical prostatectomy. The predictive value of the selected biomarkers was validated by qPCR-based methods using tissue samples extracted from the 58 prostates and, separately, using 227 prostate core biopsies. RESULTS: HOXC6, AMACR and PCA3 expression showed the best discrimination between PCa and BPH. All three genes were previously reported as the most promising mRNA-based markers for distinguishing cancerous lesions from benign prostate lesions; however, none were sufficiently sensitive and specific to meet the criteria for a PCa diagnostic biomarker. By contrast, DNA methylation levels of the APC, TACC2, RARB, DGKZ and HES5 promoter regions achieved high discriminating sensitivity and specificity, with area under the curve (AUCs) reaching 0.95-1.0. Only a small overlap was detected between the DNA methylation levels of PCa-positive and PCa-negative needle biopsies, with AUCs ranging between 0.854 and 0.899. CONCLUSIONS: DNA methylation-based biomarkers reflect the prostate malignancy and might be useful in supporting clinical decisions for suspected PCa following an initial negative prostate biopsy.
Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Transcriptoma , Proteína da Polipose Adenomatosa do Colo/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores Tumorais/metabolismo , Biópsia , Proteínas de Transporte/genética , Diacilglicerol Quinase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Próstata/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Curva ROC , Receptores do Ácido Retinoico/genética , Proteínas Repressoras/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
The epidemiology of Bartonella species infecting Apodemus flavicollis and Myodes glareolus in a forest in Eastern Poland was followed for 2 years using mark-recapture. Infections could be acquired in any month, but prevalence, and probability of infection, peaked in the summer. There were significant differences in the pattern of infections between the two species. Both hosts were primarily infected as juveniles, but the probability of infection was highest for A. flavicollis, which, evidence suggests, experienced longer-lasting infections with a wider range of Bartonella genotypes. There was no evidence of increased host mortality associated with Bartonella, although the infection did affect the probability of recapture. Animals could become re-infected, generally by different Bartonella genotypes. Several longer lasting, poorly resolved infections of A. flavicollis involved more than 1 genotype, and may have resulted from sequential infections. Of 22 Bartonella gltA genotypes collected, only 2 (both B. grahamii) were shared between mice and voles; all others were specific either to A. flavicollis or to M. glareolus, and had their nearest relatives infecting Microtus species in neighbouring fields. This heterogeneity in the patterns of Bartonella infections in wild rodents emphasizes the need to consider variation between both, host species and Bartonella genotypes in ecological and epidemiological studies.
Assuntos
Arvicolinae/microbiologia , Infecções por Bartonella/veterinária , Bartonella/genética , Murinae/microbiologia , Doenças dos Roedores/epidemiologia , Animais , Arvicolinae/classificação , Bartonella/classificação , Bartonella/isolamento & purificação , Infecções por Bartonella/epidemiologia , Infecções por Bartonella/microbiologia , Citrato (si)-Sintase/genética , Ecologia , Feminino , Genótipo , Masculino , Murinae/classificação , Polônia/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , Doenças dos Roedores/microbiologia , Estações do Ano , Especificidade da Espécie , ÁrvoresRESUMO
The heterogeneous nuclear ribonucleoprotein K (hnRNP K) protein is an RNA-binding protein involved in many processes that compose gene expression. K protein is upregulated in the malignant processes and has been shown to modulate the expression of genes involved in mitogenic responses and tumorigenesis. To explore the possibility that there are alternative isoforms of K protein expressed in colon cancer, we amplified and sequenced K protein mRNA that was isolated from colorectal cancers as well as from normal tissues surrounding the tumours. Sequencing revealed a single G-to-A base substitution at position 274 that was found in tumours and surrounding mucosa, but not in individuals that had no colorectal tumour. This substitution most likely reflects an RNA editing event because it was not found in the corresponding genomic DNAs. Sequencing of RNA from normal colonic mucosa of patients with prior resection of colorectal cancer revealed only the wild-type K protein transcript, indicating that G274A isoform is tumour related. To our knowledge, this is the first example of an RNA editing event in cancer and its surrounding tissue, a finding that may offer a new diagnostic and treatment marker.