Publications by authors named "Sónia Pires Celeiro"

3 Publications

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Reproduction of the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) Gastric Cancer Molecular Classifications and Their Association with Clinicopathological Characteristics and Overall Survival in Moroccan Patients.

Dis Markers 2021 28;2021:9980410. Epub 2021 Jul 28.

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.

Introduction: The Cancer Genome Atlas (TCGA) project and Asian Cancer Research Group (ACRG) recently categorized gastric cancer into molecular subtypes. Nevertheless, these classification systems require high cost and sophisticated molecular technologies, preventing their widespread use in the clinic. This study is aimed to generating molecular subtypes of gastric cancer using techniques available in routine diagnostic practice in a series of Moroccan gastric cancer patients. In addition, we assessed the associations between molecular subtypes, clinicopathological features, and prognosis.

Methods: Ninety-seven gastric cancer cases were classified according to TCGA, ACRG, and integrated classifications using a panel of four molecular markers (EBV, MSI, E-cadherin, and p53). HER2 status and PD-L1 expression were also evaluated. These markers were analyzed using immunohistochemistry (E-cadherin, p53, HER2, and PD-L1), in situ hybridization (EBV and HER2 equivocal cases), and multiplex PCR (MSI).

Results: Our results showed that the subtypes presented distinct clinicopathological features and prognosis. EBV-positive gastric cancers were found exclusively in male patients. The GS (TCGA classification), MSS/EMT (ACRG classification), and E-cadherin aberrant subtype (integrated classification) presented the Lauren diffuse histology enrichment and tended to be diagnosed at a younger age. The MSI subtype was associated with a better overall survival across all classifications (TCGA, ACRG, and integrated classification). The worst prognosis was observed in the EBV subtype (TCGA and integrated classification) and MSS/EMT subtype (ACRG classification). . We reported a reproducible and affordable gastric cancer subtyping algorithms that can reproduce the recently recognized TCGA, ACRG, and integrated gastric cancer classifications, using techniques available in routine diagnosis. These simplified classifications can be employed not only for molecular classification but also in predicting the prognosis of gastric cancer patients.
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http://dx.doi.org/10.1155/2021/9980410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342151PMC
January 2022

Microsatellite Instability Analysis in Gastric Carcinomas of Moroccan Patients.

Genet Test Mol Biomarkers 2021 Feb;25(2):116-123

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.

To investigate correlations between microsatellite instability (MSI) and the phenotype, clinicopathological features, and overall survival (OS) in Moroccan gastric cancer (GC) patients. We evaluated the mutation frequency of 22 MSI-target genes in MSI-positive tumors. MSI evaluation were performed for 97 gastric tumors by multiplex polymerase chain reaction (PCR) using a panel of five quasimonomorphic mononucleotide repeat markers (NR27, NR21, NR24, BAT25, and BAT26). The mutation profiles of 22 MSI-target genes were assessed by multiplex PCR and genotyping. Kaplan-Meier curves, the log-rank test, and the Cox proportional hazard regression model were used to conduct survival analyses. Microsatellite stable (MSS) status was observed in 77/97 (79.4%) gastric cancer samples, MSI-Low in 7 (7.2%) samples, and MSI-High (MSI-H) in 13 (13.4%) cases. The MSI-H phenotype was significantly associated with older age ( = 0.004), tumor location ( < 0.001), and intestinal-type of Lauren classification ( < 0.001). Among the 22 MSI target genes analyzed, the most frequently altered genes were (84.6%), (30.8%), (23.1%), (23.1%), and (23.1%). Multivariate analysis revealed the MSS phenotype (Hazard ratio, 0.23; 95% confidence interval, 0.7-7.4;  = 0.014) as an independent indicator of poor prognosis in our population. This study is the first analysis of MSI in Moroccan GC patients. MSI-H GCs have distinct clinicopathological features and an improved OS. We have identified candidate target genes altered in MSI-positive tumors with potential clinical implications. These findings can guide immunotherapy designed for Moroccan GC patients.
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http://dx.doi.org/10.1089/gtmb.2020.0146DOI Listing
February 2021

Loss of SPINT2 expression frequently occurs in glioma, leading to increased growth and invasion via MMP2.

Cell Oncol (Dordr) 2020 Feb 7;43(1):107-121. Epub 2019 Nov 7.

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.

Purpose: High-grade gliomas (HGG) remain one of the most aggressive tumors, which is primarily due to its diffuse infiltrative nature. Serine proteases and metalloproteases are known to play key roles in cellular migration and invasion mechanisms. SPINT2, also known as HAI-2, is an important serine protease inhibitor that can affect MET signaling. SPINT2 has been found to be frequently downregulated in various tumors, whereby hypermethylation of its promoter appears to serve as a common mechanism. Here, we assessed the clinical relevance of SPINT2 expression and promoter hypermethylation in pediatric and adult HGG and explored its functional role.

Methods: A series of 371 adult and 77 pediatric primary HGG samples was assessed for SPINT2 protein expression (immunohistochemistry) and promoter methylation (methylation-specific PCR) patterns. After SPINT2 knockdown and knock-in in adult and pediatric HGG cell lines, a variety of in vitro assays was carried out to determine the role of SPINT2 in glioma cell viability and invasion, as well as their mechanistic associations with metalloprotease activities.

Results: We found that SPINT2 protein expression was frequently absent in adult (85.3%) and pediatric (100%) HGG samples. The SPINT2 gene promoter was found to be hypermethylated in approximately half of both adult and pediatric gliomas. Through functional assays we revealed a suppressor activity of SPINT2 in glioma cell proliferation and viability, as well as in their migration and invasion. These functions appear to be mediated in part by MMP2 expression and activity.

Conclusions: We conclude that dysregulation of SPINT2 is a common event in both pediatric and adult HGG, in which SPINT2 may act as a tumor suppressor.
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http://dx.doi.org/10.1007/s13402-019-00475-7DOI Listing
February 2020
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