Potential link between dioxin induced progression of diffuse large B-cell lymphoma: New insights from machine learning and in vitro experiments.

[BACKGROUND] Dioxin has emerged as a major and modifiable determinant of tumor burden worldwide. Building on this premise, we investigated whether dioxin-interacting genes (DIGs) are connected to diffuse large B-cell lymphoma (DLBCL) and sought genes that might function as molecular bridges between exposure and clinical outcome.

[METHODS] DIGs were gathered (based on the Comparative Toxicogenomics Database) for differential expression analysis and combined univariable Cox regression with Least Absolute Shrinkage and Selection Operator (LASSO) to screen for DIGs robustly associated with overall survival in DLBCL. A multigene risk equation was trained in the GSE10846 cohort and evaluated in an external GSE181063 cohort. In parallel, we compared biological pathways, tumor immune contexture, and drug sensitivity between risk strata, and profiled signature genes at single‑cell resolution. Finally, independent clinical sample queue and in vitro experiments confirmed the potential therapeutic value of DIGs in DLBCL.

[RESULTS] 3 DIGs (CCT5, INHBA and PTPRF) were identified as genes associated with the prognosis of DLBCL. A prognostic risk model for DLBCL patients was constructed based on 3 DIGs. The independent dataset confirms the diagnostic value of the prognostic model. High‑risk and low‑risk groups displayed distinct immune infiltration patterns, and the three genes correlated with multiple immune lineages. An independent clinical sample cohort confirmed the differential expression of CCT5 in DLBCL. Cell experiments have confirmed CCT5 can affect DLBCL cells' function significantly.

[CONCLUSION] Our analysis delineates a plausible link between DIGs and DLBCL outcome, nominating CCT5 as environmentally relevant biomarkers with prognostic and potential therapeutic implications.