High serum C3 complement levels were associated with poor prognosis of angioimmunoblastic T-cell lymphoma (AITL)

Abstract

Abstract Background ： Angioimmunoblastic T-cell lymphoma (AITL), a distinct subtype of peripheral T-cell lymphoma (PTCL), presents with unique clinical features and poor prognosis. Primarily affecting elderly patients, AITL demonstrates aggressive disease progression characterized by systemic manifestations including progressive lymphadenopathy, hepatosplenomegaly, fever, skin lesions, anemia, and hypergammaglobulinemia. Although generally associated with poor outcomes, AITL exhibits significant heterogeneity. Identifying biomarkers linked to its prognosis holds crucial clinical significance for therapeutic guidance. C3 complement acts as potent inflammatory mediators and chemokines that induce myeloid cells to adopt tumor-promoting phenotypes (e.g., TANs and TAMs) within the tumor microenvironment. The downstream component C5a of the C3 complement system serves as a critical immunosuppressive factor that promotes angiogenesis and metastasis. C3 complement may therefore emerge as a novel prognostic risk factor for AITL. Purpose ： To explore the independent prognostic factors of AITL and provide real world evidence for clinical diagnosis and treatment. Method ： We retrospectively analyzed multicenter 350 patients with AITL treated from 4 medical centers, from August 2015 to November 2023. Through univariate analysis, smoothing curve analysis, threshold effect analysis, and multivariate regression analysis, we explored the impact of C3 complement levels on progression-free survival (PFS) and overall survival (OS). ROC analysis further demonstrated the enhanced predictive value of C3 complement levels in multiple existing prognostic scoring systems. Results： We retrospectively analyzed multicenter 350 AITL patients from multicenter , and univariate analysis demonstrated that C3 complement levels were associated with both PFS and OS at p<0.0001. Smooth curve analysis further confirmed that higher C3 complement levels corresponded to poorer PFS and OS outcomes. Threshold effect analysis revealed that in model 1 (full sample), C3 complement levels correlated with worse PFS and OS, with effects becoming more pronounced below cutoffs of 120 mg/dl (for PFS) and 118 mg/dl (for OS). Multivariate regression analysis confirmed C3 complement as an independent prognostic factor for both PFS and OS. ROC analysis further demonstrated that elevated C3 complement levels improved predictive value compared to existing prognostic scoring systems, including IPI, PIT, PIAI_RISK, AITL score (2021 Blood), and AITL score (2022 Chinese). The AUC values were 0.748 vs. 0.751,0.713 vs. 0.721,0.677 vs. 0.688,0.640 vs. 0.676, and 0.665 vs. 0.672, respectively. Conclusion ： Serum C3 complement levels were independent prognostic factors for PFS and OS, and improved the predictive value of several previous prognostic scoring systems, including IPI, PIT, PIAI_RISK, AITL score (2021 Blood), and AITL score (2022 China) prognostic scoring systems. Keyword ： Angioimmunoblastic T-cell lymphoma (AITL), C3 complement, prognosis score, PFS, OS