Abstract 97P
Background
Rheumatic and musculoskeletal diseases (RMDs) and malignancies are both caused by a dysfunctional immune system. Research on this immunological intersection offers the opportunity for better patient centred care and scientific progress. Herein, a diagnostic classification model based on changes in serum metabolome was explored for its suitability for early diagnosis of a concomitant malignancy in RMD patients.
Methods
Serum samples from patients with concomitant RMD and cancer (n=79, breast cancer (14), melanoma (13), MGUS (11) and others (41)) were collected within the MalheuR project. The groups were defined by the underlying RMD and matched with controls (n=123) without malignancies: rheumatoid arthritis (RA, 42 vs. 48), psoriatic arthritis (PsA, 25 vs. 43) and spondyloarthritis (SpA, n=12 vs. 32). Samples were analysed by 1H NMR spectroscopy. Molar concentrations of 28 metabolites were acquired by integration of NMR spectra and compared by univariate and ANOVA statistical analyses.
Results
Mean disease duration was 11.5±10.4 years for cancer and 12.5±11.1 years for RMDs since diagnosis. At sample collection, 5 vs. 0% received cancer treatment, 41 vs. 38% glucocorticoids and 76 vs. 84% any disease modifying anti-rheumatic drug in the malignancy versus control groups. Concentrations of amino acids H, T, N, K, R, V and L as well as short chain fatty acids and tricarboxylic acid cycle intermediates were considerably reduced in all malignancy samples. Some amino acids (D, A, I, Y, Q, E, F, G) were reduced only in certain RMD entities. Only in RA, four metabolite concentrations (glutamine, formate, creatinine, citrate) were significantly higher in the malignancy group. No significant differences in the metabolome were observed between the malignancy groups.
Conclusions
Significant differences between the metabolomic fingerprints of RMD patients with and without malignancies could be observed. These changes might be characteristic for cancer burden, as the underlying RMD was not relevant when comparing the concentrations between the malignancy groups. Our results may promote understanding of the interrelationships of both disease entities as well as prove useful as biomarkers for diagnostic and therapeutic purposes.
Clinical trial identification
MalheuR Project S-391/2018 IRB University of Heidelberg.
Editorial acknowledgement
Legal entity responsible for the study
Academic Group at Heidelberg University Hospital, Medicine V.
Funding
University of Heidelberg.
Disclosure
D. Marx, K. Benesova, M. Souto-Carneiro: Financial Interests, Institutional, Research Grant: Grant/research support from medical faculty (Olympia Morata Program) and foundations commission (Herbert Daus estate) of University of Heidelberg. All other authors have declared no conflicts of interest.