Polymer degradation product-related candidate genes are associated with prognostic and immune heterogeneity in multiple myeloma

While polyethylene (PE), polystyrene (PS), and polyvinyl chloride (PVC) polymers and their environmental degradation products have been implicated in the pathogenesis of various diseases, their specific roles in multiple myeloma (MM) remain poorly understood. This study aims to identify candidate genes associated with polymer degradation product-related signatures and to evaluate their prognostic value in MM. The analysis is based on the overlap between MM-related genes and computationally predicted polymer targets; it does not directly demonstrate exposure or causality. First, differential expression analysis and WGCNA were undertaken in the GSE39754 dataset to acquire differentially expressed genes (DEGs) and WGCNA genes. Second, PE, PS, and PVC target genes were acquired from public databases. Subsequently, intersection of 3 gene sets was taken to acquire candidate genes. Prognostic genes were further recognized through univariate Cox regression analysis and machine learning, and risk model was constructed. Additionally, molecular regulatory networks, molecular docking, and molecular dynamics (MD) simulations were undertaken. Finally, potential biological mechanisms of MM were explored at the single-cell level. The expression levels of prognostic genes were detected using reverse transcription quantitative PCR (RT-qPCR) technology. PTGS1, CA1, and SYK were recognized as prognostic genes. Risk model exhibited robust predictive performance. Additionally, 225 and 138 pathways were associated with LRC and HRC, respectively. CA1 presented a strong positive correlation with type 17 T helper cells. Computational prediction suggested that NEAT1 and SNHG6 might regulate CA1 through hsa-miR-944. Molecular docking predicted weak-to-moderate binding affinity between representative degradation products/monomers of PE, PS, and PVC and the prognostic genes, and MD simulation explored the stability of the predicted PTGS1–PS complex. These in silico results are hypothesis-generating and require experimental validation. Finally, single-cell analysis identified macrophages as a key MM-associated cell population, and SYK displayed dynamic expression trends in pseudotime analysis. These findings are exploratory and do not directly link macrophages to polymer exposure. PCR results revealed that the mRNA expression levels of CA1 and PTGS1 in the MM group were significantly downregulated, whereas SYK showed no significant difference ( P < 0.05 for CA1 and PTGS1). In vitro, exposure to PE/PVC microspheres (1 μm) altered PTGS1 mRNA expression but increased CA1 and SYK mRNA expression in MM cell lines; CA1 silencing attenuated polymer-induced cell death and improved cell viability. The direction of PTGS1 change was consistent between clinical samples and cell lines, whereas CA1 was downregulated in clinical samples but upregulated after acute polymer exposure. These cell-line findings suggest a potential role for CA1 in polymer-induced cytotoxicity, but they do not establish a causal link to MM progression. This study provides candidate genes and a prognostic framework for further investigation of potential links between polymer degradation products and MM. It does not establish a causal role for PE, PS, or PVC in MM pathogenesis.