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1.
Int J Cancer ; 140(1): 176-187, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27632639

RESUMO

Circulating microRNAs (miRNAs) have been proposed as minimally invasive prognostic markers for various types of cancers, including colorectal cancer (CRC), the third most diagnosed cancer worldwide. We aimed to evaluate the levels of circulating miRNAs that might serve as markers for CRC prognosis and survival. We included plasma samples of 543 CRC patients with stage I-IV disease from a population-based study carried out in Germany. After comprehensive evaluation of current literature, 95 miRNAs were selected and measured with Custom TaqMan® Array MicroRNA Cards. Plasma samples of non-metastatic and metastatic colon cancer patients, each group consisting of ten patients with 'good' and ten patients with 'bad' prognosis were screened. Identified candidate miRNAs were further validated by RT-qPCR in the whole study cohort. The association of the miRNA levels with patients' survival and the prognostic subtypes was analyzed with uni- and multivariate logistic regression and Cox proportional hazards regression models. Increased miR-122 levels were associated with a 'bad' prognostic subtype in metastatic CRC (Odds ratio: 1.563, 95% confidence interval (CI): 1.038-2.347) and a shorter relapse-free survival and overall survival for non-metastatic (Hazard ratio (HR): 1.370, 95% CI: 1.028-1.825; HR: 1.353, 95% CI: 1.002-1.828) and metastatic (HR: 1.264, 95% CI: 1.050-1.520; HR: 1.292, 95% CI: 1.078-1.548) CRC patients. Additionally, several members of the miR-200 family showed associations with patients' prognosis and correlations to clinicopathological characteristics. The here identified miRNA markers, miR-122 and the miR-200 family members, could be of use in the development of a multi-marker blood test for CRC prognosis.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , MicroRNAs/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Família Multigênica , Metástase Neoplásica , Prognóstico , Análise de Sobrevida
2.
Exp Mol Pathol ; 99(1): 180-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26112095

RESUMO

Triple-negative breast cancer (TNBC) is a group of very aggressive breast tumours, characterised by lack of expression of oestrogen receptor (ER), progesterone receptor (PR) and erb-b2 receptor tyrosine kinase 2 (ERBB2/HER2). Nevertheless, TNBCs show different clinical characteristics and are very diverse regarding prognostic outcome. So far, only a few prognostic markers for TNBC have been reported that could be helpful for therapeutic stratification. Here we have analysed the expression of S100P and HYAL2 using immunohistochemistry (IHC) in a TNBC cohort of 98 patients with a follow-up for recurrence and death. TNBC patients with high expression of both proteins showed significantly shorter progression-free survival (PFS) (mean PFS=35.9months, P=0.001) compared to TNBC patients with high expression levels of only one of the proteins (mean PFS=69.4months) and to TNBC patients with low expression of both proteins (mean PFS=83.3months). Moreover, multivariate Cox-regression model showed the combined expression of S100P and HYAL2 as independent prognostic factor for PFS (P=0.001). The expression of S100P and HYAL2 indicated similar prognostic effect to the overall survival (OS) of TNBC patients. In addition, high expression levels of both S100P and HYAL2 showed significant association with different clinicopathological characteristics, such as more recurrence events (P=0.004), and higher occurrence of metastasis (P=0.002). Our study proposes S100P and HYAL2 as potential prognostic markers for TNBC.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Moléculas de Adesão Celular/metabolismo , Hialuronoglucosaminidase/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Biomarcadores Tumorais/genética , Proteínas de Ligação ao Cálcio/genética , Moléculas de Adesão Celular/genética , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Hialuronoglucosaminidase/genética , Imuno-Histoquímica , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/terapia
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