Abstract 4432: Molecular biomarkers of non-Hodgkin lymphomas and subtypes identified by mass spectrometry-based metabolomics
Authors: Choueiry Fouad , Singh Satishkumar , Sehgal Lalit , Zhu Jiangjiang (Chris) 
Published: March 2024

Non-Hodgkin lymphomas (NHLs) constitute a diverse collection of lymphoid neoplasms, each characterized by distinct biological features. Approximately 90% of all lymphomas in the United States stem from B lymphocytes, with the remainder originating from T cells. The therapeutic approach for NHLs hinges on the neoplastic histology and the tumor stage, guiding the determination of whether radiotherapy, chemotherapy, or a combination thereof represents the most effective treatment strategy. Following an indolent phase, 50% of patients experience disease transformation into an aggressive form of lymphoma, leading to rapid deterioration and patient demise. While extensive efforts have been directed towards understanding the genetics of transformation, the contribution of altered tumor metabolism, induced by these genetic lesions, to disease aggressiveness remains unclear. Therefore, there exists an urgent need to better understand the metabolic changes during lymphoma transformation and treatment. Given the metabolic adaptations supporting bioenergetics, biosynthesis, and redox in malignant cells, here in this study we aimed to identify unique metabolic signatures in prominent lymphoma subsets—diffuse large B-cell (DLBCL), mantle cell (MCL), and follicular lymphomas (FL). Employing unbiased mass spectrometry-based metabolomics, we screened sera samples from n=30 patients with lymphoma and n=25 aged and BMI-matched healthy controls for molecular biomarkers that may be indicative of the subtypes. Principal component analysis revealed distinct clustering of the disease and control groups, indicating unique metabolic profiles induced by lymphoma presence. A total of 36 metabolites, including adenine, trans-aconitic acid, and citric acid, were significantly deregulated between groups (FC &gt; 2, FDR p &lt; 0.05). Functionally, enriched pathways included tryptophan metabolism and the tricarboxylic cycle (FDR p &lt; 0.05), supporting our previous findings that lymphomas rely on oxidative phosphorylation for sustained proliferation. Comparing metabolic profiles of different lymphomas subtypes demonstrated unique clustering, emphasizing the distinct metabolic flexibility of each malignancy. Interestingly, cystine was the primary metabolite driving separation of the groups in our partial least squares discriminant analysis (PLS-DA), with DLBCLs demonstrating the highest abundance of this amino acid. In summary, our research uncovered that there are distinctive metabolic shifts resulting from the transformation of lymphomas. The findings stemming from our unbiased metabolic screening enables a better understanding of the complex metabolic intricacies in lymphomas and paves the way for prominent biomarker detection for improved patient outcomes.

Citation Format: Fouad Choueiry, Satishkumar Singh, Lalit Sehgal, Jiangjiang (Chris) Zhu. Molecular biomarkers of non-Hodgkin lymphomas and subtypes identified by mass spectrometry-based metabolomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4432.