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. 2024 Nov 12;14(1):27714.
doi: 10.1038/s41598-024-79176-7.

ACVR2B polymorphism, Adiponectin, and GDF-15 levels as biomarkers for cachexia in gastrointestinal cancer

Laura de Martin Coletti  1 , Gabriela Gonzalez Segura  1 , Leticia Cangemi Guedes de Freitas  1 , Jackeline de Souza Rangel Machado  2 , Rene Beleboni  1 , Adilson Faccio  3 , Mozart Marins  1 , Ana Lúcia Fachin  4   5
Affiliations

ACVR2B polymorphism, Adiponectin, and GDF-15 levels as biomarkers for cachexia in gastrointestinal cancer

Laura de Martin Coletti et al. Sci Rep. .

Abstract

Reversing cancer cachexia remains a challenge. Genetic biomarkers for the early detection of the disease have been explored in order to enable the implementation of preventive measures. We therefore genotyped candidate genes based on cachexia phenotype and quantified adiponectin and GDF-15 levels in cachectic patients with gastrointestinal cancer. Patients with a diagnosis of gastrointestinal cancer were divided into a cachectic and a non-cachectic group after the start of chemotherapy. A control group (no cancer) was also included. We genotyped the following single nucleotide polymorphisms (SNPs) by quantitative PCR: FOXO3 (rs1935949), FOXO3 (rs4946935), ACVR2B (rs2268757), and SELP (rs6136). In addition, we quantified adiponectin and GDF-15 levels by ELISA. The rs2268757 SNP in the ACVR2B gene was associated with the weight loss phenotype in cachectic patients with gastrointestinal cancer (non-cachectic, P = 0.004). Plasma adiponectin levels were higher in cachectic patients compared to controls (P = 0.01) and non-cachectic patients (P = 0.004). GDF-15 was also elevated in cachectic patients compared to controls (P < 0.0001) and non-cachectic patients (P = 0.001). Analysis by sex showed elevated adiponectin levels in men (control, P = 0.01) and cachectic women (control, P = 0.04; non-cachectic, P = 0.01), as well as elevated GDF-15 levels in men (control, P = 0.002) and cachectic women (control, P = 0.002; non-cachectic, P = 0.007). However, there was no significant difference in the levels of these cytokines between cachectic men and women. The results suggest the rs2268757 SNP in the ACVR2B gene, adiponectin, and GDF-15 as potential biomarkers of cachexia in gastrointestinal cancer.

Keywords: Adiponectin; Cachexia; Chemotherapy; Gastrointestinal cancer; Polymorphism.

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Conflict of interest statement

Declarations Ethics approval and consent to participate This study was approved by the Research Ethics Committee of the University of Ribeirão Preto (UNAERP) (protocol number 5.968.150), São Paulo, Brazil. Written informed consent was obtained from all participants in the study. Competing interests The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Comparison of adiponectin (A) and GDF-15 (B) levels between control, (n = 51), non-cachectic (n = 25), and cachectic patients (n = 45). Kruskal-Wallis test.
Fig. 2
Fig. 2
Correlation between plasma levels of adiponectin (A) and GDF-15 (B) and weight loss percentage after chemotherapy in cachectic patients (n = 49). Spearman correlation.
Fig. 3
Fig. 3
Comparison of plasma levels of adiponectin (A) and GDF-15 (B) between the control, non-cachectic and cachectic groups according to sex. Two-way ANOVA.
See this image and copyright information in PMC

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