This research is aimed to explore the molecular response of the skin cells to Hidradenitis Suppurativa (HS). Microarray transcriptome data for patients with HS, merged and employed to identify the differentially expressed genes (DEGs), gene ontology (GO), and long non-coding RNAs (lncRNAs). A protein-protein interaction network, and consequently, a co-expression network, was constructed for the essential genes. The key genes' clinical relevance was also established by survival analysis, relative expression level, immunohistochemistry, and immune infiltration correlation analysis. Finally, potential herbal ingredients with inhibitory effects on cancer inducer proteins were characterized using the Traditional Chinese Medicine (TCMD) database. The chemokine signaling pathway was the gene ontology of the most significant cluster found by clusterONE. Myocardial Infarction Associated Transcript (MIAT) and RNA Polymerase II Subunit J4, Pseudogene (POLR2J4) are the predicted lncRNAs for up-and down-regulated genes. Interleukin 6 (IL6), Formyl Peptide Receptor 2 (FPR2), C-X-C Motif Chemokine Ligand 10 (CXCL10), C-C Motif Chemokine Receptor 7 (CCR7), and C-C Motif Chemokine Ligand 5 (CCL5) genes were predicted as hub-genes. Tryptophan 2,3-Dioxygenase (TDO2), Serpin Family B Member 4 (SERPINB4), and Matrix Metallopeptidase 3 (MMP3) were demonstrated to be potential cancer inducers due to their high expression level in HS disease. These genes also were positively correlated with dendritic cells, T cell CD4+, monocytes, and neutrophils in the skin cancer microenvironment. Piceatannol, Salicylic acid, and magnolol herbal ingredients were predicted as potential compounds with inhibitory effects on SERPIN B4, MMP3, and TDO2, respectively. The output of the present study will aid in a better understanding of the HS disease and consequent cancer induction mechanism.
