In a groundbreaking study, published in Annals of the Rheumatic Diseases researchers have identified a set of metabolic markers in the blood that can indicate the presence of paraneoplasia (PN) or concomitant cancer in patients suffering from rheumatic musculoskeletal diseases (RMDs). This discovery promises to revolutionize the timely diagnosis of cancer in these patients, who often experience diagnostic delays due to overlapping symptoms.
The study meticulously quantified metabolic changes in the sera of rheumatoid arthritis (RA) patients with (n=56) and without (n=52) a history of invasive cancer using nuclear magnetic resonance analysis. The analysis revealed that specific concentrations of acetate, creatine, glycine, formate, and the lipid ratio L1/L6 could effectively distinguish between cancerous and non-cancerous states. The diagnostic model developed from these markers exhibited exceptionally high sensitivity and specificity for cancer diagnosis, with an area under the curve (AUC) of 0.995 in the model cohort, 0.940 in the blinded RA validation cohort, and 0.928 in the mixed RA/SpA cohort. Notably, the model also demonstrated its capability to identify cancer in patients with paraneoplastic syndromes, proving insensitive to common demographic or clinical confounders and non-invasive malignancies like non-melanoma skin cancer.
Previous research has shown that metabolic profiles of RA patients can be determined using targeted and non-targeted metabolomics technology. These profiles reveal changes in glucose, lipid, and amino acid levels, involved in various metabolic pathways including glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, the arachidonic acid metabolic pathway, and amino acid metabolism. These alterations in metabolic pathways and metabolites can meet bio-energetic demands, enhance cell proliferation, stimulate the secretion of inflammatory mediators, facilitate leukocyte infiltration, and contribute to joint destruction and muscle atrophy. These processes reflect the underlying etiologies of rheumatoid arthritis (RA). Differential metabolites can serve as biomarkers for diagnosis, prognosis, and risk prediction, thereby enhancing the specificity and accuracy of diagnostic and prognostic evaluations.
This innovative set of metabolic markers shows great promise in accurately predicting the presence of cancer in patients with arthritis or PN, with high sensitivity and specificity. The implications of this study are profound, as it holds the potential to significantly accelerate and improve the accuracy of cancer diagnosis in RMD patients, ultimately leading to better patient outcomes and survival rates. As this diagnostic model continues to undergo further validation and refinement, it may soon become an indispensable tool in the clinical setting, offering hope for more timely and precise cancer diagnoses in a patient population that has long faced diagnostic challenges.
References
- Gente K, Feisst M, Marx D, Klika KD, Christopoulos P, Graf J, et al. Altered serum metabolome as an indicator of paraneoplasia or concomitant cancer in patients with rheumatic disease. Ann Rheum Dis. 2024 Jul 15;83(8):974–983.
- Xu L, Chang C, Jiang P, Wei K, Zhang R, Jin Y et al. Metabolomics in rheumatoid arthritis: Advances and review. Front Immunol. 2022 Aug 11;13:961708.