Serum IL‐35 levels is a new candidate biomarker of cancer‐related cachexia in stage IV non‐small cell lung cancer

BACKGROUND: Cancer‐related cachexia is a major cause of treatment resistance and poor prognosis, which is characterized by anorexia and skeletal muscle depletion. To date, there have been no reports on the relationship between IL‐35 and cancer‐related cachexia in patients with stage IV non‐small cell lung cancer. METHODS: Serum IL‐35 levels in 86 patients with stage IV NSCLC were measured and statistically analyzed based on patients' clinicopathological parameters. Serum albumin levels, C‐reactive protein, and skeletal muscle index (SMI) of the patients were also determined. In vivo studies using a mouse model were also conducted by subcutaneously injecting immunodeficiency (SCID) mice with overexpressing IL‐35 cell lines and determining their daily food intake, bodyweight and muscle atrophy. Cachexia indicators were measured again after administering the mice with an anti‐IL35 neutralizing antibody. RESULTS: Patients with stage IV NSCLC had significantly higher serum IL‐35 levels than the healthy controls. Similarly, circulating IL‐35 levels were significantly higher in patients with cachexia than those without. The SMI values of patients with high serum IL‐35 levels were significantly lower than those with low serum IL‐35 levels. Mice subcutaneously injected with LLC PLV‐IL‐35 cell lines exhibited anorexia, weight loss, and muscle atrophy. Moreover, these symptoms were significantly reduced after administering the mice with an anti‐IL35 neutralizing antibody. CONCLUSIONS: This study reveals that high serum IL‐35 expression is associated with non‐small cell lung cancer cachexia and skeletal muscle atrophy. These findings highlight its potential as a biomarker and therapeutic target for controlling cachexia of advanced lung cancer.