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The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia

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Published on: November 30, 2016

Circulating Inflammatory and Mitochondrial Biomarkers Associated with Cachexia in Advanced Non-Small Cell Lung

Kamya Sankar¹, Elham Kazemian¹, Nicole Lorona¹

¹Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

|February 27, 2026

Summary

Biomarkers like GDF-15 and IL-15 may predict cancer-associated cachexia in non-small cell lung cancer (NSCLC) patients early on. Later, increased mitochondrial DNA (mtDNA) levels indicate cachexia progression, suggesting potential for early detection.

Keywords:

biomarkers cachexia mitochondrial DNA non-small cell lung cancer

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Area of Science:

Biochemistry
Oncology
Metabolic Syndrome

Background:

Cancer-associated cachexia affects 40% of non-small cell lung cancer (NSCLC) patients, causing significant muscle and adipose tissue loss.
Current methods lack reliable circulating biomarkers for early detection and risk stratification of cachexia in NSCLC.
Mitochondrial DNA (mtDNA) and inflammatory markers are hypothesized to predict cachexia development and progression.

Purpose of the Study:

To investigate the association between plasma biomarkers and the onset and progression of cachexia in patients with advanced NSCLC.
To identify potential circulating biomarkers for early detection and risk stratification of cancer-associated cachexia.

Main Methods:

Plasma samples from 27 stage IV NSCLC patients were collected at two time points.
Forty biomarkers, including inflammatory proteins and mtDNA, were quantified using a multiplexed MesoScale Discovery platform.
Firth's penalized logistic regression was used to analyze associations between biomarker levels and cachexia status.

Main Results:

Cachectic patients showed lower body mass index at both time points.
Early in disease (T1), elevated GDF-15 and IL-15 levels were strongly associated with cachexia, while IL-4 showed a protective effect.
Later (T2), increased circulating mtDNA levels correlated with cachexia, alongside decreased levels of IL-15, IL12/IL23p40, and MDC.

Conclusions:

Distinct inflammatory and mitochondrial biomarkers can track the evolution of cachexia in advanced NSCLC.
Early elevations in GDF-15 and IL-15, followed by increased circulating mtDNA, may serve as indicators of cachexia.
Further longitudinal studies are needed to validate these biomarkers and establish their clinical utility in NSCLC management.