Cytokine-Cytokine Receptor Interaction and Endocytosis are Common Pathways for Symptom Burden and Sickness Behavior...

Inflammation is associated with sickness behavior symptoms in patients receiving chemotherapy. However, its impact on symptom burden (i.e., higher number of concurrent symptoms) requires evaluation. Study purposes were to evaluate for differentially perturbed immune and/or inflammatory pathways between outpatients receiving chemotherapy with Low (i.e., 0-8) versus High (i.e., 16-38) symptom burden and identify common immune and/or inflammatory pathways among symptom burden and single sickness behavior symptoms.

Prior to their second or third cycle of chemotherapy, oncology outpatients reported the occurrence of 38 symptoms using the Memorial Symptom Assessment Scale and provided a peripheral blood sample. Using previously identified symptom cutpoints, patients with Low versus High symptom burden were evaluated. Transcriptome-wide gene expression was quantified using RNA-sequencing (n = 213; RNA-seq sample) or microarray (n = 207; microarray sample) technologies. Pathway impact analyses (PIA) were performed and signaling pathways were defined with the Kyoto Encyclopedia of Genes and Genomes database. Fisher's combined probability test was used to identify perturbed pathways between the Low and High symptom burden groups across both samples (false discovery rate < 0.005).

For the RNA-seq sample, 159 patients had High and 54 patients had Low symptom burden. For the microarray sample, 135 patients had High and 72 patients had Low symptom burden. Of the 40 pathways that were perturbed between the Low and High symptom burden groups, 10 were involved in immune or inflammatory processes. Cytokine-cytokine receptor interaction and endocytosis pathways were the common pathways identified across this study and PIAs of single sickness behavior symptoms.

This study is the first to identify differentially perturbed immune and inflammatory signaling pathways that were associated with symptom burden in oncology patients receiving chemotherapy. Evaluation of interventions targeted at the cytokine-cytokine receptor interaction and endocytosis pathways may decrease the burden associated with single and multiple occurring symptoms.