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Chemotherapy-induced fatigue is associated with changes in gene expression in the peripheral blood mononuclear cell fraction of patients with locoregional breast cancer

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Abstract

Purpose

Chemotherapy-induced fatigue (CIF) is a frequent symptom that impairs patient functioning and quality of life. We aimed to evaluate whether systemic chemotherapy can induce a specific gene expression profile in peripheral blood mononuclear cells (PBMNC) of patients with locoregional breast cancer (LRBC) who develop CIF.

Methods

PBMNC were collected from 3 patients who developed CIF before and after their initial cycle of chemotherapy, and RNA-seq was performed in an Ion Torrent™ System. A total of 12.345 transcripts were sequenced, of which 26 were selected out of 71 that had significantly different expression before and after chemotherapy. The RNA-seq results were validated by RT-qPCR in a different group of 28 patients with LRBC who developed CIF after their first cycle of chemotherapy and in six patients who also received chemotherapy but did not develop CIF (controls). We assessed CIF according the BFI and Chalder Questionnaires.

Results

We observed a significant increase in expression of DUSP18 and RHOBTB1 and decreased expression of NCAN and RAET1G in patients who developed CIF after chemotherapy. Control patients only exhibited a significant decrease in NCAN expression.

Conclusion

CIF induces specific changes in gene expression in the PBMNC of LRBC patients. Some of these changes, such as downregulation of NCAN expression, may reflect direct effects of chemotherapy since they are also observed in the controls. Furthermore, CIF may involve downregulation of skeletal muscle genes (RHOBT1, DUSP18) and immune systems (RAETG1), whereas NCAN downregulation may underlie the adverse cognitive effects of chemotherapy.

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Funding

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP grant no. 2014/08322-0).

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Authors and Affiliations

  1. Faculdade de Medicina do ABC, Av. Príncipe de Gales, 821, Santo André, SP, ZIP 09060-650, Brazil

    Barbara Bonaparte Ribas de Alcântara, Felipe Melo Cruz, Fernando Luiz Affonso Fonseca, Beatriz da Costa Aguiar Alves, Matheus Moreira Perez, Daniel de Iracema Gomes Cubero & Auro Del Giglio

  2. Institute of Pharmaceutical Sciences, Universidade Federal de São Paulo, R. Prof. Artur Riedel, 275, Diadema, SP, ZIP 09972-270, Brazil

    Fernando Luiz Affonso Fonseca

  3. Center for Research and Molecular Diagnosis of Genetic Diseases, Department of Biophysics-Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

    Patricia Varela & João Bosco Pesquero

  4. Centro de Oncologia do ABC, Rua Catequese, 199, Santo André, SP, ZIP 09090-401, Brazil

    Daniel de Iracema Gomes Cubero

  5. Hospital Anchieta, R. Silva Jardim 470, São Bernardo do Campo, SP, ZIP 09715-090, Brazil

    Claudia Vaz De Melo Sette

Authors
  1. Barbara Bonaparte Ribas de Alcântara
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  2. Felipe Melo Cruz
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  10. Auro Del Giglio
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Corresponding author

Correspondence to Auro Del Giglio.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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de Alcântara, B.B.R., Cruz, F.M., Fonseca, F.L.A. et al. Chemotherapy-induced fatigue is associated with changes in gene expression in the peripheral blood mononuclear cell fraction of patients with locoregional breast cancer. Support Care Cancer 27, 2479–2486 (2019). https://doi.org/10.1007/s00520-018-4519-0

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