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

Thorac Cancer. 2022 Mar;13(5):716-723. doi: 10.1111/1759-7714.14307. Epub 2022 Feb 9.

Abstract

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.

Keywords: IL-35; SMI; cachexia; skeletal muscle atrophy; stage IV NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Cachexia / etiology
  • Cachexia / pathology
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Humans
  • Interleukins / therapeutic use
  • Lung Neoplasms* / complications
  • Lung Neoplasms* / pathology
  • Mice

Substances

  • Biomarkers
  • Interleukins