Abstract 872: Pathogenesis underlying the bidirectional relationship between non-Hodgkin lymphomas and primary Sjögren's Syndrome

Abstract

Abstract Introduction: Bidirectional relationship between non-Hodgkin lymphomas (NHLs) and Sjögren's syndrome (SS) has been recognized in large scale cohort studies. To investigate the underlying pathogenesis of this association, we identified highly expressed genes and altered pathways with RNA-sequencing (RNA-seq) data from SS and NHLs patients. Methods: Canonical pathway analysis was conducted by comparing RNA-seq data from whole-transcriptome expression profiling to identify underlying pathogenesis among NHL patients with Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL), and SS patients. Collected biopsies included lymphoma biopsies for NHLs, including BL (n = 59), DLBCL (n = 88), FL (n = 65), MCL (n = 43), and MZL (n = 23), sorted B cells from healthy donors (n=10), as well as parotid gland tissues for SS (n=17). Fold changes and z-scores were derived after normalized by the expression levels among controls. RNA-seq data with P values less than 0.05 or -log10(P) values larger than 1.3 were considered significantly expressed. Positive z-scores indicated up-regulation while negative z-scores indicated down-regulation. Results: There were 17 identified significantly expressed genes (P < 0.05 for all NHLs and SS), including well-known cancer-associated genes CXCL13, COL1A1, IGFBP7, COL3A1, CXCL9, CXCL12, CCL19, and CLU. Among them, CXCL13 was the most expressed gene involved in NHLs and SS. The fold changes of CXCL13 were 14.09, 465.57, 319.51, 369.70, 817.63, and 4.03 for BL, DLBCL, FL, MCL, MZL, and SS, respectively. Among all identified pathways underlying SS and NHL development, which were ordered based on the sum of z-scores, the endocannabinoid system-driven cancer inhibition pathways were the most significantly altered in both SS and NHLs, followed by interferon-involved antiviral responses, when compared to matched healthy controls. The z-scores of the cancer inhibition pathways were -0.14 for BL (-log10(P) = 4.54), -1.30 for DLBCL (-log10(P) = 3.00), -0.33 for FL (-log10(P) = 4.67), -0.87 for MCL (-log10(P) =3.77), -2.61 for MZL (-log10(P) = 4.31), and -1 for SS (-log10(P) = 1.44). Conclusion: The underlying pathogenesis for SS-associated NHL development involved 17 highly expressed genes, including CXCL13, and down-regulated cancer inhibition pathways. Citation Format: Kevin Sheng-Kai Ma, Cho-Han Chiang, Li-Tzu Wang. Pathogenesis underlying the bidirectional relationship between non-Hodgkin lymphomas and primary Sjögren's Syndrome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 872.