Amostras dos lisados OSNA permitem estabelecer uma assinatura metastática transcricional em doentes com carcinoma da mama com recetores hormonais positivos em estadios precoces

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Amostras dos lisados OSNA permitem estabelecer uma assinatura metastática transcricional em doentes com carcinoma da mama com recetores hormonais positivos em estadios precoces

Quarta, 14.12.2022

O OSNA (One Step Nucleic Acid Amplification) é uma técnica recente para o estadiamento dos gânglios sentinela em doentes com cancro da mama. Após a análise OSNA, o excedente do lisado OSNA, em vez de ser descartado, pode ser utilizado para estudos de expressão génica, sendo potencialmente a amostra ideal para pesquisa de novos biomarcadores. O objetivo do nosso estudo foi identificar biomarcadores relacionados com a interação tumor-microambiente nos lisados OSNA dos gânglios sentinela em mulheres com cancro da mama com recetores hormonais positivos em estadios precoces. Nos gânglios sentinela metastáticos identificamos 11 genes diferencialmente expressos (superexpressos). Estes genes codificam proteínas principalmente envolvidas na agressividade tumoral e com impacto na resposta imune. Assim, estes achados reforçam que a análise transcriptómica dos lisados OSNA poderá, no futuro, ser útil para estratificação prognóstica e seleção terapêutica. Dado que a tecnologia OSNA está a ser implementada para estadiamento ganglionar noutros tipos de cancro, esta abordagem poderá ter uma utilidade ainda mais abrangente.

 

Autores e afiliações:

Inês Gante 1,2,3,Joana Martins Ribeiro 4, João Mendes 3,4, Ana Gomes 5, Vânia Almeida 5,6, Frederico Soares Regateiro 3,7,8, Francisco Caramelo 3,9,10, Henriqueta Coimbra Silva 3,4,10 and Margarida Figueiredo-Dias 1,2,3 

1 Gynecology Department, Coimbra Hospital and Universitary Centre (CHUC), 3004-561 Coimbra, Portugal
2 University of Coimbra, Gynecology University Clinic, Faculty of Medicine, 3000-548 Coimbra, Portugal
3 Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
4 Laboratory of Sequencing and Functional Genomics of UCGenomics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
5 Department of Pathology, Coimbra Hospital and Universitary Centre (CHUC), 3004-561 Coimbra, Portugal
6 Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
7 Allergy and Clinical Immunology Unit, Coimbra Hospital and Universitary Centre (CHUC), 3004-561 Coimbra, Portugal
8 Institute of Immunology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
9 Laboratory of Biostatistics and Medical Informatics (LBIM), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
10 Center for Innovative Biomedicine and Biotechnology (CIBB), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
 

Abstract:

The One Step Nucleic Acid Amplification (OSNA) is being adopted worldwide for sentinel lymph nodes (SLNs) staging in breast cancer (BC). As major disadvantage, OSNA precludes prognostic information based on structural evaluation of SLNs. Our aim is to identify biomarkers related to tumor-microenvironment interplay exploring gene expression data from the OSNA remaining lysate. This study included 32 patients with early stage hormone receptors-positive BC. Remaining OSNA lysates were prepared for targeted RNA-sequencing analysis. Identification of differentially expressed genes (DEGs) was performed by DESeq2 in R and data analysis in STATA. The results show that, in metastatic SLNs, several genes were upregulated: KRT7, VTCN1, CD44, GATA3, ALOX15B, RORC, NECTIN2, LRG1, CD276, FOXM1 and IGF1R. Hierarchical clustering analysis revealed three different clusters. The identified DEGs codify proteins mainly involved in cancer aggressiveness and with impact in immune response. The overexpression of the immune suppressive genes VTCN1 and CD276 may explain that no direct evidence of activation of immune response in metastatic SLNs was found. We show that OSNA results may be improved incorporating microenvironment-related biomarkers that may be useful in the future for prognosis stratification and immunotherapy selection. As OSNA assay is being implemented for SLNs staging in other cancers, this approach could also have a wider utility.

 

Revista: Cancers

 

Linkhttps://www.mdpi.com/2072-6694/14/23/5855