FLAVIA REGINA ROTEA MANGONE
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
2 resultados
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- A gene expression profile related to immune dampening in the tumor microenvironment is associated with poor prognosis in gastric adenocarcinoma(2014) PASINI, Fatima Solange; ZILBERSTEIN, Bruno; SNITCOVSKY, Igor; ROELA, Rosimeire Aparecida; MANGONE, Flavia R. Rotea; RIBEIRO JR., Ulysses; NONOGAKI, Suely; BRITO, Glauber Costa; CALLEGARI, Giovanna D.; CECCONELLO, Ivan; ALVES, Venancio Avancini Ferreira; ELUF-NETO, Jose; CHAMMAS, Roger; FEDERICO, Miriam Hatsue HondaThe TNM Classification of Malignant Tumours (TNM) staging system is the primary means of determining a prognosis for gastric adenocarcinoma (GC). However, tumor behavior in the individual patient is unpredictable and in spite of treatment advances, a classification of 'advanced stage' still portends a poor prognosis. Thus, further insights from molecular analyses are needed for better prognostic stratification and determination of new therapeutic targets. A total of fifty-one fresh frozen tumor samples from patients with histopathologically confirmed diagnoses of GC, submitted to surgery with curative intent, were included in the study. Total RNA was extracted from an initial group of fifteen samples matched for known prognostic factors, categorized into two subgroups, according to patient overall survival: poor (< 24 months) or favorable (at or above 24 months), and hybridized to Affymetrix Genechip human genome U133 plus 2.0 for genes associated with prognosis selection. Thirteen genes were selected for qPCR validation using those initial fifteen samples plus additional thirty-six samples. A total of 108 genes were associated with poor prognosis, independent of tumor staging. Using systems biology, we suggest that this panel reflects the dampening of immune/inflammatory response in the tumor microenvironment level and a shift to Th2/M2 activity. A gene trio (OLR1, CXCL11 and ADAMDEC1) was identified as an independent marker of prognosis, being the last two markers validated in an independent patient cohort. We determined a panel of three genes with prognostic value in gastric cancer, which should be further investigated. A gene expression profile suggestive of a dysfunctional inflammatory response was associated with unfavorable prognosis.
- Four-gene expression model predictive of lymph node metastases in oral squamous cell carcinoma(2012) PASINI, Fatima Solange; MAISTRO, Simone; SNITCOVSKY, Igor; BARBETA, Lilian P.; MANGONE, Flavia R. Rotea; LEHN, Carlos N.; WALDER, Fernando; CARVALHO, Marcos B.; BRENTANI, M. Mitzi; FEDERICO, Miriam H. H.Background. Previous knowledge of cervical lymph node compromise may be crucial to choose the best treatment strategy in oral squamous cell carcinoma (OSCC). Here we propose a set four genes, whose mRNA expression in the primary tumor predicts nodal status in OSCC, excluding tongue. Material and methods. We identified differentially expressed genes in OSCC with and without compromised lymph nodes using Differential Display RT-PCR. Known genes were chosen to be validated by means of Northern blotting or real time RT-PCR (qRT-PCR). Thereafter we constructed a Nodal Index (NI) using discriminant analysis in a learning set of 35 patients, which was further validated in a second independent group of 20 patients. Results. Of the 63 differentially expressed known genes identified comparing three lymph node positive (pN+) and three negative (pN0) primary tumors, 23 were analyzed by Northern analysis or RT-PCR in 49 primary tumors. Six genes confirmed as differentially expressed were used to construct a NI, as the best set predictive of lymph nodal status, with the final result including four genes. The NI was able to correctly classify 32 of 35 patients comprising the learning group (88.6%; p = 0.009). Casein kinase 1alpha1 and scavenger receptor class B, member 2 were found to be up regulated in pN + group in contrast to small proline-rich protein 2B and Ras-GTPase activating protein SH3 domain-binding protein 2 which were upregulated in the pN0 group. We validated further our NI in an independent set of 20 primary tumors, 11 of them pN0 and nine pN+ with an accuracy of 80.0% (p = 0.012). Conclusions. The NI was an independent predictor of compromised lymph nodes, taking into the consideration tumor size and histological grade. The genes identified here that integrate our ""Nodal Index"" model are predictive of lymph node metastasis in OSCC.