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

Autor(es)

Ribas de Alcantara, Barbara Bonaparte ^[1] ; Cruz, Felipe Melo ^[1] ; Affonso Fonseca, Fernando Luiz ^{[1, 2]} ; Aguiar Alves, Beatriz da Costa ^[1] ; Perez, Matheus Moreira ^[1] ; Varela, Patricia ^[3] ; Pesquero, Joao Bosco ^[3] ; Gomes Cubero, Daniel de Iracema ^{[1, 4]} ; De Melo Sette, Claudia Vaz ^[5] ; Del Giglio, Auro ^[1]

Afiliação do(s) autor(es)

^[1] Fac Med ABC, Ave Principe Gales 821, BR-09060650 Santo Andre, SP - Brazil

^[2] Univ Fed Sao Paulo, Inst Pharmaceut Sci, R Prof Artur Riedel 275, BR-09972270 Diadema, SP - Brazil

^[3] Univ Fed Sao Paulo, Escola Paulista Med, Dept Biophys, Ctr Res & Mol Diag Genet Dis, Sao Paulo - Brazil

^[4] Ctr Oncol ABC, Rua Catequese 199, BR-09090401 Santo Andre, SP - Brazil

^[5] Hosp Anchieta, R Silva Jardim 470, BR-09715090 Sao Bernardo Do Campo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SUPPORTIVE CARE IN CANCER; v. 27, n. 7, p. 2479-2486, JUL 2019.
• Citações Web of Science: 1

Resumo

PurposeChemotherapy-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.MethodsPBMNC 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.ResultsWe 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.ConclusionCIF 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. (AU)

• Processo FAPESP: 14/08322-0 - Avaliação de biomarcadores de fadiga em pacientes com câncer de mama submetidas à quimioterapia antineoplásica adjuvante através de análise de transcriptoma
• Beneficiário: Auro del Giglio
• Modalidade de apoio: Auxílio à Pesquisa - Regular