Pain, fatigue, and associated gene expressions over chemotherapy in patients with colorectal cancer

Abstract

Context Patients with colorectal cancer undergoing chemotherapy often experience significant pain and fatigue. Limitations in understanding the complex phenotypes and biological mechanisms of these symptoms hinder effective interventions. Objectives This study aimed to identify the pain and fatigue patterns during one chemotherapy cycle and associated gene expression profiles. Method In a prospective longitudinal study, 34 patients with colorectal cancer from a major cancer center in the Northeastern US were recruited. Self-reported outcome measures of pain and fatigue and blood samples were collected at baseline, post-chemotherapy, and at the end of the chemotherapy cycle. RNA sequencing followed by differential expression analysis identified changes in gene expression. Linear mixed models examined associations between symptoms and possible biomarkers over time. Results The sample had a mean age of 58.4 years old, with 97% being white and non-Hispanic. Among participants, 44.1% had stage III cancer, and 26.5% were undergoing initial chemotherapy. Abdominal pain was the most frequently reported symptom. Fatigue levels significantly worsened post-chemotherapy (P = 0.011) and after recovery (P = 0.018). Critical pathways involved inflammatory response and myeloid cell development (FDR<5%). Mixed-effect linear regression analysis revealed statistically significant associations between the upregulation of LILRA6 and higher pain interference (β=−6.621, p=0.010) and fatigue (β=−6.621, p=0.010), as well as between the downregulation of CACNG6 (β=−1.043, p=0.047) and PRSS33 upregulation (β=1.384, p=0.038) and increased pain interference. Given the small sample size, these findings should be interpreted with caution. Conclusion These findings suggest inflammation and specific biomarkers may drive pain and fatigue during chemotherapy. Further preclinical models or clinical cohorts are needed to validate these results and explore potential implications for targeted interventions to reduce symptom burden in patients with colorectal cancer.