Browsing by Author "Silva, Marco"
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- Methylation patterns in dysplasia in inflammatory bowel disease patientsPublication . Rosa, Isadora; Silva, Patricia; da Mata, Sara; Magro, Fernando; Carneiro, Fatima; Peixoto, Armando; Silva, Marco; Sousa, Helena Tavares; Roseira, Joana; Parra, Jose; Barosa, Rita; Vieira, Ana; Brito, Maria Jos; Lago, Paula; Coelho, Andre; Moleiro, Joana; da Silva, Joao Pereira; Fonseca, Ricardo; Albuquerque, Cristina; Dias Pereira, A.Background and aims:Inflammatory Bowel Disease (IBD) with colonic involvement increases colorectal cancer risk. However, the distinction between IBD related and sporadic dysplasia in IBD patients is difficult. Some data favors the importance of abnormal DNA methylation in IBD-related carcinogenesis. We aimed to define methylation patterns in patients with colonic cancer or dysplasia diagnosis following an IBD diagnosis. Methods:Multicentric cross-sectional study-91 samples from colonic mucosa with/without dysplasia from 9 patients with IBD-related dysplasia/cancer and 26 patients with IBD and sporadic dysplasia/cancer were included. Methylation patterns of CpG islands in the promoter regions of 67 genes were studied by Methylation-specific Multiplex Ligation-dependent Probe Amplification. Results:Mean age at IBD diagnosis: 42 +/- 16 years;at dysplasia diagnosis: 56 +/- 14 years. Twenty-ninepatients had ulcerative colitis. Twenty-five patients had at least 1 lesion endoscopically described as adenoma-like, 4 at least 1 non-adenoma like, 3 had cancer and 3 had dysplasia in flat mucosa. No patient had both adenoma-like and non-adenoma-like lesions. Patients with an IBD-related lesion were significantly younger at IBD diagnosis (p = .003) and at dysplasia/cancer diagnosis (p = .039). Promoter methylation ofIGF2, RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1genes was significantly associated to dysplasia/cancer; methylation ofMSH6, TIMP3was significantly associated to IBD-related dysplasia/cancer. Promoter methylation ofMSH6, MSH3, RUNX3, CRABP1, TP73, RARB, CDH13, PAX5, WT1, THBS1, TP53, SFRP1, WIF1, APAF1,BCL2genes was significantly associated to active IBD. Conclusions:Methylation analysis, namely ofMSH6, may contribute to the classification of dysplastic lesions in IBD- to be further tested in prospective studies.
- Soluble human Suppression of Tumorigenicity 2 is associated with endoscopic activity in patients with moderate-to-severe ulcerative colitis treated with golimumabPublication . Magro, Fernando; Lopes, Susana; Silva, Marco; Coelho, Rosa; Portela, Francisco; Branquinho, Diogo; Correia, Luís; Fernandes, Samuel; Cravo, Marília; Caldeira, Paulo; Sousa, Helena Tavares; Patita, Marta; Lago, Paula; Ramos, Jaime; Afonso, Joana; Redondo, Isabel; Machado, Patrícia; Philip, George; Lopes, Joanne; Carneiro, FátimaSuppressor of Tumorigenicity 2 (ST2) is an IL33 receptor detected in the mucosa and serum of ulcerative colitis (UC) patients. We evaluated soluble ST2 (sST2) as a surrogate biomarker of disease outcome and therapeutic response, in moderate-to-severe UC patients treated with golimumab.