Research Papers:

Distinct pattern of one-carbon metabolism, a nutrient-sensitive pathway, in invasive breast cancer: A metabolomic study

Jéssica Reis Santos _, Dan Linetzky Waitzberg, Ismael Dale Cotrim Guerreiro da Silva, Tharcisio Citrangulo Tortelli Junior, Luciana Rodrigues Carvalho Barros, Gisele André Baptista Canuto, Andréa Tedesco Faccio, Lydia Fumiko Yamaguchi, Massuo Jorge Kato, Marina Franco Maggi Tavares, Ana Cristina Martinez, Ângela Flavia Logullo, Raquel Suzana M.M. Torrinhas and Graziela Ravacci

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Oncotarget. 2020; 11:1637-1652. https://doi.org/10.18632/oncotarget.27575

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Jéssica Reis Santos1, Dan Linetzky Waitzberg1, Ismael Dale Cotrim Guerreiro da Silva2, Tharcisio Citrangulo Tortelli Junior3, Luciana Rodrigues Carvalho Barros3, Gisele André Baptista Canuto5, Andréa Tedesco Faccio4, Lydia Fumiko Yamaguchi4, Massuo Jorge Kato4, Marina Franco Maggi Tavares4, Ana Cristina Martinez1, Ângela Flavia Logullo2, Raquel Suzana M.M. Torrinhas1 and Graziela Ravacci1

1 Gastroenterology Department, University of São Paulo School of Medicine (FMUSP), São Paulo, Brazil

2 Gynecology Department, College of Medicine of the Federal University of São Paulo (EPM-UNIFESP), São Paulo, Brazil

3 Centro de Investigação Translacional em Oncologia (LIM24), Departamento de Radiologia e Oncologia, Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil

4 Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil

5 Departamento de Química Analítica, Instituto de Química, Universidade Federal da Bahia, Salvador, Brazil

Correspondence to:

Jéssica Reis Santos,email: [email protected]

Keywords: invasive ductal carcinoma; targeted metabolomics; untargeted metabolomics; tumor metabolism; one-carbon metabolism

Received: February 25, 2019     Accepted: April 03, 2019     Published: May 05, 2020


Altered cell metabolism is a hallmark of cancer and critical for its development. Particularly, activation of one-carbon metabolism in tumor cells can sustain oncogenesis while contributing to epigenetic changes and metabolic adaptation during tumor progression. We assessed whether increased one-carbon metabolism activity is a metabolic feature of invasive ductal carcinoma (IDC). Differences in the metabolic profile between biopsies from IDC (n = 47) and its adjacent tissue (n = 43) and between biopsies from different breast cancer subtypes were assessed by gas spectrometry in targeted (Biocrates Life Science®) and untargeted approaches, respectively. The metabolomics data were statistically treated using MetaboAnalyst 4.0, SIMCA P+ (version 12.01), Statistica 10 software and t test with p < 0.05. The Cancer Genome Atlas breast cancer dataset was also assessed to validate the metabolomic profile of IDC. Our targeted metabolomics analysis showed distinct metabolomics profiles between IDC and adjacent tissue, where IDC displayed a comparative enrichment of metabolites involved in one-carbon metabolism (serine, glycine, threonine, and methionine) and a predicted increase in the activity of pathways that receive and donate carbon units (i.e., folate, methionine, and homocysteine). In addition, the targeted and untargeted metabolomics analyses showed similar metabolomics profiles between breast cancer subtypes. The gene set enrichment analysis identified different transcription-related functions between IDC and non-tumor tissues that involved one-carbon metabolism. Our data suggest that one-carbon metabolism may be a central pathway in IDC and even in general breast tumors, representing a potential target for its treatment and prevention.

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