Additionally, prior studies have hypothesized that other RAGE proteins may play a role in emphysema pathogenesis [55, 56], including HMGB1 (a transcription enhancer, cytokine, and inflammation promoter) [57] and protein S100-A12 (an alarmin released by activated neutrophils and monocytes in inflammatory responses) [58]; our GO and Reactome pathway enrichment results support their involvement. Here, HMGB1 is linked to pulmonary emphysema.