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糖尿病、糖尿病周围神经病变及癌症辅助治疗中针灸靶点与免疫基因的综合分析

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

作者信息

Zhang Quan-Ai, Luo Wang-Sheng, Li Ji, Zhang Qi-Wen, Guo Qin, Chen Jian, Liang Zhi-Qiang

机构信息

The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.

Department of Cardiology, the First Affiliated Hospital of University of South China, Hengyang, People's Republic of China.

出版信息

J Multidiscip Healthc. 2024 Oct 28;17:4939-4962. doi: 10.2147/JMDH.S483940. eCollection 2024.

DOI:10.2147/JMDH.S483940
PMID:39492981
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11529286/
Abstract

INTRODUCTION

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.

摘要

引言

针灸可能有助于治疗糖尿病（DM）、糖尿病周围神经病变（DPN）以及作为癌症的辅助治疗，但其中涉及的生物学机制和免疫相关基因尚不清楚；本研究旨在阐明这些方面。

方法

综合基因表达分析揭示了DM、DPN和对照样本之间的差异表达基因（DEG）。将来自加权基因共表达网络分析（WGCNA）的关键基因与DEG和针灸靶点进行交叉分析。研究了炎症反应、免疫过程、信号通路、免疫细胞浸润以及微小RNA-基因相互作用。分析了枢纽免疫相关基因失调与拷贝数变异和基因甲基化的关系。创建了一个泛癌列线图模型，基于各种因素预测生存情况，将枢纽基因与癌症特征联系起来。

结果

我们的分析在DM/对照和DPN/DM比较中分别发现了3217个和2191个DEG，并确定了1830个潜在的针灸靶点。我们在DM中确定了21个关键基因，在DPN中确定了43个关键基因，这些基因参与炎症反应、免疫过程、钙调神经磷酸酶激酶2（CAMKK2）和环磷酸腺苷（cAMP）信号通路。注意到不同的免疫细胞浸润模式，包括M0和M2巨噬细胞、中性粒细胞和滤泡辅助性T细胞。进一步分析揭示了在两种情况下与免疫枢纽基因相互作用的微小RNA和转录因子（TF）基因。八个枢纽免疫相关基因的失调与拷贝数变异和基因甲基化有关，与癌症预后相关。在这些基因中观察到单核苷酸变异和致癌突变的共现。泛癌列线图模型显示出强大的预后能力，并且发现这八个基因与血管生成、上皮-间质转化（EMT）和细胞周期进程等癌症特征之间存在显著关联。

讨论

我们的研究结果强调了丝裂原活化蛋白激酶3（MAPK3）、白细胞介素1受体拮抗剂（IL1RN）、超氧化物歧化酶2（SOD2）、组织蛋白酶D（CTSD）、雌激素受体1（ESR1）、溶质载体家族1成员1（SLC1A1）、神经肽Y（NPY）和C-C趋化因子受体2（CCR2）在DM、DPN以及癌症辅助治疗背景下针灸介导的免疫反应中的关键作用。

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