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

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.