Sarcopenia, a hallmark of cancer cachexia, is linked to an unfavorable prognosis in several malignancies. This study investigated the role of sarcopenia as an independent prognostic factor in lung cancer patients with malignant pleural effusion (MPE) and explored the potential underlying mechanisms using metabolomics. Clinical data from 393 lung cancer patients with MPE at Wuhan Union Hospital from January 2016 to September 2021 were analyzed retrospectively. Univariate and multivariate analyses were used to evaluate the prognostic significance of skeletal muscle and adipose tissue measurements obtained from computed tomography scans of the fourth thoracic vertebra (T4) and third lumbar vertebra. Additionally, metabolomic profiling of pleural fluid from 84 patients was performed, and the effects of candidate metabolites were validated in vitro and in vivo . The T4 skeletal muscle area (T4-SMA) served as an independent prognostic indicator for overall survival in lung cancer patients with MPE. Based on their T4-SMA, patients were categorized into sarcopenia and non-sarcopenia groups using sex-specific cutoff values. Metabolomic analysis identified 61 differential metabolites between sarcopenic and non-sarcopenic patients, with significant sex-based differences. Pathway analysis suggested disruptions in amino acid and unsaturated fatty acid metabolism. Furthermore, arachidonic acid was found to induce muscle atrophy by activating multiple signaling pathways associated with inflammation and sarcopenia. These findings indicate that sarcopenia is an independent prognostic factor in lung cancer with MPE. Alterations in fatty acid and amino acid metabolism, as well as inflammation, may contribute to the potential mechanisms underlying sarcopenia.
Xia et al. (Sun,) studied this question.