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. 2024 Aug 30;16(17):3035.
doi: 10.3390/cancers16173035.

Salivary Interleukin-13 and Transforming Growth Factor Beta as Potential Biomarkers of Cancer Cachexia

Borislav Belev  1   2 , Ivan Vičić  1 , Filip Sedlić  2 , Matko Prtorić  2 , Majana Soče  1 , Juraj Prejac  1   3 , Slavica Potočki  4 , Tajana Silovski  1   2 , Davorin Herceg  1   3 , Ana Kulić  1
Affiliations

Salivary Interleukin-13 and Transforming Growth Factor Beta as Potential Biomarkers of Cancer Cachexia

Borislav Belev et al. Cancers (Basel). .

Abstract

Cancer cachexia is a syndrome characterized by weight and muscle loss and functional impairment, strongly influencing survival in cancer patients. In this study, we aimed to establish the role of saliva cytokine measurement in cancer cachexia investigation and define two potential independent salivary biomarkers of the condition.

Methods: serum and saliva specimens were obtained from 78 patients. Forty-six patients were non-cachectic, and 32 patients were cachectic (per SCRINIO group criteria), all with metastatic solid tumors. Commercial ELISA kits were used to determine the salivary and serum concentrations of interleukin 13 (IL-13) and transforming growth factor beta (TGF-β) in two patient groups and healthy controls. Laboratory values were obtained from the hospital information system, and weight and height were measured at the time of sampling.

Results: A statistically significant difference was observed between the groups in saliva IL-13 concentrations but no difference in serum concentrations. Statistically significant differences were also observed between the groups in saliva and serum concentrations of TGF-β. Logistic regression analysis has identified salivary IL-13 and TGF-β as independent factors for cancer cachexia.

Conclusions: We demonstrated saliva as a valuable specimen for cachexia investigation and established IL-13 and TGF-β as potential cancer cachexia biomarkers. Further research is needed to evaluate these findings.

Keywords: IL-13; TGF-ß; biomarker; cancer cachexia; cancer metabolism; cytokines; saliva.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
(a) The effects and signaling of TGF-β. Canonical signaling results in a change of gene transcription, which exerts specific effects; (b) The effects and signaling of IL-13. Through STAT3 signaling and possibly another, so far undefined mechanism, IL-13 exhibits its metabolic effects. TGF-βR—transforming growth factor beta receptor; RyR—ryanodine receptor; NOX 4—NADPH oxidase 4; ROS—reactive oxygen species; MAPK—mitogen-activated protein kinase; EMT—epithelial-mesenchymal transition; Err—estrogen-related receptor; IL-4R—interleukin-4 receptor; IL-13R—interleukin-13 receptor; STAT 3—signal transducer and activator of transcription 3.
Figure 1
Figure 1
(a) The effects and signaling of TGF-β. Canonical signaling results in a change of gene transcription, which exerts specific effects; (b) The effects and signaling of IL-13. Through STAT3 signaling and possibly another, so far undefined mechanism, IL-13 exhibits its metabolic effects. TGF-βR—transforming growth factor beta receptor; RyR—ryanodine receptor; NOX 4—NADPH oxidase 4; ROS—reactive oxygen species; MAPK—mitogen-activated protein kinase; EMT—epithelial-mesenchymal transition; Err—estrogen-related receptor; IL-4R—interleukin-4 receptor; IL-13R—interleukin-13 receptor; STAT 3—signal transducer and activator of transcription 3.
Figure 2
Figure 2
Concentrations of IL-13 and TGF-β in serum and saliva of patients with malignant diseases and healthy controls. (a) Summary data of serum and saliva IL-13 concentrations in healthy control (H) and malignant diseases (P); (b) Summary data of serum and saliva TGF-β in healthy control (H) and malignant diseases.
Figure 3
Figure 3
(a) correlation of IL-13 levels in serum and saliva; (b) correlation of TGF-β levels in serum and saliva.
Figure 4
Figure 4
Correlation of IL-13 and TGF-β levels in patients with malignant diseases. (a) saliva (significant correlation); (b) serum (no correlation).
Figure 5
Figure 5
Concentrations of IL-13 and TGF-β in serum and saliva of non-cachectic (NC) and cachectic patients (C). (a) summary data of serum IL-13 concentrations; (b) summary data of serum TGF-β concentrations; (c) summary data of saliva IL-13 concentrations; (d) summary data of saliva TGF-β concentrations.
Figure 6
Figure 6
ROC curve analysis. (a) AUC of serum IL-13; (b) AUC of saliva IL-13.
Figure 7
Figure 7
ROC curve analysis. (a) AUC of serum TGF-β; (b) AUC of saliva TGF-β.
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