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Cancer- and cardiac-induced cachexia: same fate through different inflammatory mediators?

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Abstract

Background

Inflammation is widely recognized as the driving force of cachexia induced by chronic diseases; however, therapies targeting inflammation do not always reverse cachexia. Thus, whether inflammation per se plays an important role in the clinical course of cachectic patients is still a matter of debate.

Aims

To give new insights into cachexia’s pathogenesis and diagnosis, we performed a comprehensive literature search on the contribution of inflammatory markers to this syndrome, focusing on the noncommunicable diseases cancer and cardiovascular diseases.

Methods

A systematic review was performed in PubMed using the keywords (“cancer” OR “cardiac” cachexia AND “human” OR “patient” AND “plasma” or “serum”). A total of 744 studies were retrieved and, from these, 206 were selected for full-text screening. In the end, 98 papers focusing on circulating biomarkers of cachexia were identified, which resulted in a list of 113 different mediators.

Results

Data collected from the literature highlight the contribution of interleukin-6 (IL-6) and C-reactive protein (CRP) to cachexia, independently of the underlying condition. Despite not being specific, once the diagnosis of cachexia is established, CRP might help to monitor the effectiveness of anti-cachexia therapies. In cardiac diseases, B-type natriuretic peptide (BNP), renin, and obestatin might be putative markers of body wasting, whereas in cancer, growth differentiation factor (GDF) 15, transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) C seem to be better markers of this syndrome. Independently of the circulating mediators, NF-κB and JAK/STAT signaling pathways play a key role in bridging inflammation with muscle wasting; however, therapies targeting these pathways were not proven effective for all cachectic patients.

Conclusion

The critical and integrative analysis performed herein will certainly feed future research focused on the better comprehension of cachexia pathogenesis toward the improvement of its diagnosis and the development of personalized therapies targeting specific cachexia phenotypes.

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Acknowledgements

This work was supported by “Fundação para a Ciência e a Tecnologia”—FCT, European Union, QREN, FEDER and COMPETE for funding the LAQV-REQUIMTE (UIDB/50006/2020), UnIC (UIDB/IC/00051/2020 and UIDP/00051/2020), and CIAFEL (UIDB/00617/2020) research units, RISE – Health Research Network-From the Lab to the Community (LA/P/0053/2020), ITR—Laboratory for Integrative and Translational Research in Population Health (LA/P/0064/2020) and the research projects DOCnet (NORTE-01-0145-FEDER-000003), NETDIAMOND (SAICT-PAC/0047/2015), and PROTECT (PTDC/SAU-DES/7945/2020). Rita Nogueira-Ferreira acknowledges FCT for the research contract CEECIND/03935/2021 under the CEEC Individual 2021.

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  1. UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal

    Rita Nogueira-Ferreira, Fábio Sousa-Nunes, Adelino Leite-Moreira, Liliana Moreira-Costa & Rui Vitorino

  2. Serviço de Cardiologia, Centro Hospitalar Vila Nova de Gaia/ Espinho, Porto, Portugal

    Fábio Sousa-Nunes

  3. Department of Cardiothoracic Surgery, Centro Hospitalar Universitário São João, Porto, Portugal

    Adelino Leite-Moreira

  4. iBiMED, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal

    Rui Vitorino

  5. Experimental Pathology and Therapeutics Group Research Centre, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal

    Lúcio Lara Santos

  6. CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal

    Daniel Moreira-Gonçalves

  7. ITR, Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal

    Daniel Moreira-Gonçalves & Rita Ferreira

  8. LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal

    Rita Ferreira

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Authors RNF, FSN, and LMS: performed the literature search and wrote the manuscript. RNF and RF: conceptualized the review. RF and DMG: wrote the first draft and edited the review. ALM, RV, and LLS: critically revised the work.

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Nogueira-Ferreira, R., Sousa-Nunes, F., Leite-Moreira, A. et al. Cancer- and cardiac-induced cachexia: same fate through different inflammatory mediators?. Inflamm. Res. 71, 771–783 (2022). https://doi.org/10.1007/s00011-022-01586-y

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