Integrative Analysis of Acupuncture Targets and Immune Genes in Diabetes, Diabetic Peripheral Neuropathy, and Adjunct Therapy of Cancer

Quan-Ai Zhang,1,* Wang-Sheng Luo,2,* Ji Li,3,* Qi-Wen Zhang,1 Qin Guo,1 Jian Chen,3– 5 Zhi-Qiang Liang3 1The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Cardiology, the First Affiliated Hospital of University of South China, Hengyang, People’s Republic of China; 3Department of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Anhui Province Rural Revitalization Collaborative Technical Service Center, Huangshan University, Huangshan, People’s Republic of China; 5Department of Public Health, International College, Krirk University, Bangkok, Thailand*These authors contributed equally to this workCorrespondence: Jian Chen; Zhi-Qiang Liang, Department of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200082, People’s Republic of China, Email [email protected]; [email protected]: Acupuncture may help treat diabetes mellitus (DM), diabetic peripheral neuropathy (DPN), and adjunct therapy for cancer, but the biological mechanisms and immune-related genes involved are unclear; this study aims to clarify these aspects.Methods: Comprehensive gene expression analysis revealed differentially expressed genes (DEGs) among DM, DPN, and control samples. Key genes from WGCNA were intersected with DEGs and acupuncture targets. Inflammatory responses, immune processes, signaling pathways, immune cell infiltration, and microRNA–gene interactions were studied. Hub immune-related genes’ dysregulation was analyzed for copy number variation and gene methylation. A pan-cancer nomogram model was created to predict survival based on various factors, linking hub genes to cancer properties.Results: Our analysis found 3,217 and 2,191 DEGs in DM/control and DPN/DM comparisons, respectively, and identified 1,830 potential acupuncture targets. We pinpointed 21 key genes in DM and 43 in DPN, involved in inflammatory responses, immune processes, CAMKK2, and cAMP signaling pathways. Distinct immune cell infiltration patterns, including M0 and M2 macrophages, neutrophils, and follicular helper T cells, were noted. Further analysis revealed microRNAs and TF genes interacting with immune hub genes in both conditions. Dysregulation of eight hub immune-related genes was linked to copy number variation and gene methylation, correlating with cancer prognosis. Co-occurrence of single nucleotide variations and oncogenic mutations was observed in these genes. The pan-cancer nomogram model showed strong prognostic capabilities, and a significant association was found between the eight genes and cancer properties like angiogenesis, EMT, and cell cycle progression.Discussion: Our findings underscore the pivotal roles of MAPK3, IL1RN, SOD2, CTSD, ESR1, SLC1A1, NPY, and CCR2 in the immune response mediated by acupuncture in the context of DM, DPN, and adjunct therapy for cancer. Keywords: acupuncture, text mining, network pharmacology, immune, diabetic peripheral neuropathy, cancer