POS0472 COMPARATIVE METABOLOMIC ANALYSIS OF SERUM SAMPLES FROM PATIENTS WITH COINCIDENTAL RHEUMATOLOGICAL AND MALIGNANT DISEASES
Authors: D. Marx, L. Diekmann, K. Klika, H. M. Lorenz, K. Benesova, M. Souto-Carneiro
Journal: Annals of the Rheumatic Diseases (2021)

Background: Rheumatic and musculoskeletal diseases (RMDs) and malignancies are both caused by a dysfunctional immune system and the probability of their coincidence in one individual is rising due to advances in cancer treatment and demographic changes. However, the lack of understanding of the complex interrelationship of both conditions often leads to undertreatment and high level of suffering in affected patients. Herein, the MalheuR project breaks new ground by systematic analysis of concomitant malignant and rheumatic diseases and closes the knowledge gaps on the clinical and molecular level. Objectives: To enable early diagnosis of concomitant malignancy and/or identification of patients at risk in the future, changes in serum metabolome were explored in order to create a diagnostic classification model. Methods: Serum samples from patients with concomitant RMD and cancer or obligate precancerous lesions (n=78, breast cancer (23), melanoma (14), MGUS (12), prostate cancer (8) and others (21)) were collected as a pilot study within the MalheuR project, a registry-based study initiated in 2018 at the university hospital Heidelberg, Germany. The following groups were defined by the underlying RMD: rheumatoid arthritis (n=42), psoriasis arthritis (n=23), spondylarthritis (n=9) and systemic lupus erythematosus (n=4). RMD patients without any malignancies were used as controls (n=280: 122 RA, 81 PsA, 46 SpA, 31 SLE). Samples were analyzed by 1H NMR spectroscopy. For all samples, regular 1H acquisition with presaturation and Carr-Purcell-Meiboom-Gill (CPMG) spectra were acquired using a 600 MHz Bruker NMR spectrometer. Spectra were processed with TopSpin using 0.2 Hz of line broadening and manual phasing. Molar concentrations of 26 metabolites were acquired by integration of NMR spectra. With GraphPad Prism, univariate and ANOVA statistical analysis was performed to find significant differences between each malignant group and their control group as well as between all four malignant groups. Results: Mean disease duration was 11.8 ±10.5 years for cancer and 12.8±10.8 years for RMDs since diagnosis. 1.4% received cancer treatment (6.4% of malignancy group), 69.3% csDMARDs, 42.3% b/tsDMARDs and 46.4% glucocorticoids at the time of sample collection. Most metabolites tested were significantly lower in the malignancy groups versus associated controls: Concentrations of amino acids V and L were significantly reduced in all malignancy samples. Additionally, T, D, N, Q, E, A, I were altered in RA, SpA and PsA, changes in G were seen in RA, PsA and SLE and P was altered in RA and PsA only. Furthermore, lower concentrations of short chain fatty acids and tricarboxylic acid cycle intermediates were present in the malignancy groups. In no case was a metabolite concentration significantly higher in the malignancy group than in the associated control. When comparing the metabolome within the four malignancy groups, only the concentrations of creatine, threonine and isoleucine were found higher in RA patients with malignancy. Conclusion: 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 in most cases 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. Acknowledgements: Grant/research support from medical faculty (Olympia Morata Programme) and foundations commission (Herbert Daus estate) of University of Heidelberg Disclosure of Interests: None declared