Metabolic dysregulation associated with core symptom cluster in lung cancer patients undergoing chemotherapy

Adverse symptoms are the main reason for unexpected hospital admissions in lung cancer patients. The fatigue-pain-sleep disturbance symptom cluster is the core symptom cluster among those undergoing chemotherapy, significantly affecting the clinical outcomes of patients. The mechanisms behind the core symptom cluster haven't been well understood and may relate to metabolic disorders. Understanding the related mechanisms is crucial for symptom management and patient outcomes.

One hundred lung cancer patients undergoing chemotherapy were involved in this cross-sectional study. During their third to fifth chemotherapy, they were asked to complete questionnaires that evaluated the condition of fatigue, pain, and sleep disturbance. Patients were categorized into high, moderate, and low core symptom cluster groups using the K-means algorithm. Comparison was conducted on demographic data, symptoms, and symptom interference among groups. Plasma samples from patients were collected for untargeted metabolomics, and the differential metabolites among groups were identified. Pathway enrichment analysis was performed to understand the potential mechanism of the core symptom cluster. Trend analysis was conducted on the differential metabolites to identify the significant clusters of metabolites with similar variation among groups. Receiver Operating Characteristic curves were generated to evaluate the distinguish efficacy of the metabolites panel for the core symptom cluster.

The K-means algorithm categorized 100 patients into three groups based on core symptom cluster, including 46 in low, 35 in moderate, and 19 in high. Most of the cancer-related symptoms and symptom interference were increased progressively with the severity of the core symptom cluster. The metabolomic analysis identified 1,334 annotated metabolites. The high and moderate groups showed a higher similarity in metabolic profile, yet were distinct from the low group. Choline metabolism in cancer was the highest enrichment pathway in the Kyoto Encyclopedia of Genes and Genomes analysis. Trend analysis identified a panel of 24 metabolites that increased with core symptom cluster progression, distinguishing 87.8% of patients with moderate or high severity from those with low.

This study is the first to explore the metabolic profile associated with the core symptom cluster in lung cancer, revealing significant changes in the clinical phenotypes and metabolic disorders in patients with moderate to high core symptom cluster. Dysregulated choline metabolism emerged as a key signature within the broader metabolic disturbances linked to core symptom cluster. We identified a promising panel of metabolites for diagnosing the core symptom cluster, which are expected to serve as biomarkers in the future.