RESUMO
BACKGROUND: Colorectal cancer (CRC) screening can help to reduce its incidence and mortality. Noninvasive strategies, such as plasma analysis of epigenetic alterations, can constitute important biomarkers of CRC detection. OBJECTIVE: This study aimed to evaluate the plasma methylation status of SEPT9 and BMP3 promoters as biomarkers for detection of CRC and its precursor lesions in a Brazilian population. METHODS: Plasma samples from 262 participants of the CRC screening program of Barretos Cancer Hospital who had a positive fecal occult blood test and underwent colonoscopy and cancer patients were analyzed. Participants were grouped according to the worst lesion detected in the colonoscopy. Cell-free circulating DNA (cfDNA) was bisulfite treated followed by the analysis of SEPT9 and BMP3 methylation status using a droplet digital PCR system (ddPCR). The best methylation cutoff value for group discrimination was calculated by receiver operating characteristic (ROC) curve analysis. RESULTS: Among the 262 participants, 38 were diagnosed with CRC, 46 with advanced adenomas 119 with nonadvanced adenomas, three with sessile serrated lesions, and 13 with hyperplastic polyps. In 43 participants, no lesion was detected in the colonoscopy and were used as controls. The CRC group showed the highest cfDNA concentration (10.4 ng/mL). For the SEPT9 gene, a cutoff of 2.5% (AUC = 0.681) that discriminates between CRC and the control group resulted in CRC sensitivity and specificity of 50% and 90%, respectively. Concerning the BMP3 gene, a cutoff of 2.3% (AUC = 0.576) showed 40% and 90% of sensitivity and specificity for CRC detection, respectively. Combining SEPT9, BMP3 status, and age over 60 years resulted in a better performance for detecting CRC (AUC = 0.845) than the individual gene models, yielding 80% and 81% of sensitivity and specificity, respectively. CONCLUSION: The present study suggests that a combination of SEPT9 and BMP3 plasma methylation, along with age over 60 years, showed the highest performance in detecting CRC in a Brazilian population. These noninvasive biomarkers can potentially serve as useful tools for CRC screening programs.
Assuntos
Adenoma , Ácidos Nucleicos Livres , Neoplasias Colorretais , Humanos , Pessoa de Meia-Idade , Detecção Precoce de Câncer , Brasil/epidemiologia , Metilação de DNA , Septinas/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Sensibilidade e Especificidade , Adenoma/diagnóstico , Adenoma/genética , Biomarcadores Tumorais/genética , Proteína Morfogenética Óssea 3/genéticaRESUMO
The Barretos Cancer Hospital Animal Facility (BCHAF) is a unique facility in Brazil exclusively dedicated to working with animal models for cancer research. In this article, we briefly present our modern facility and the main experiments performed, focusing on mutant strains of mice (PTCH-knockout and ApcMin mice), xenograft models, and patient-derived xenografts (PDXs). Our results show the progress and challenges in establishing these models and the need for having an appropriate representation of our cancer population to better understand tumor biology and to identify cancer biomarkers, which could be putatively targeted, allowing for personalized therapy.
RESUMO
We describe a case of sarcoid-like cutaneous paracoccidioidomycosis in a 26-year-old male, with a 10-year evolution, wrongly diagnosed as granulomatous rosacea. The correct diagnosis was only possible after the appearance of a new skin lesion with a more typical characteristic of the dermatosis, correlated with anatomopathological, laboratory and imaging exams. The clinical presentation of paracoccidioidomycosis is diverse, and the sarcoid-like form can mimic several chronic granulomatous diseases, such as sarcoidosis, tuberculoid leprosy, leishmaniasis, or tuberculosis. This presentation of cutaneous paracoccidioidomycosis is rare, and its diagnosis depends on the clinicopathological correlation, which can be a challenge for the dermatologist.