Guangdong Medical University, Zhanjiang, China.
Department of Burn Surgery, The First People's Hospital of Foshan, Foshan, China.
Front Immunol. 2022 Jul 27;13:942446. doi: 10.3389/fimmu.2022.942446. eCollection 2022.
A keloid is a fibroproliferative disorder of unknown etiopathogenesis that requires ill-defined treatment. Existing evidence indicates that the immune system plays an important role in the occurrence and development of keloid. However, there is still a lack of research on the immune-related signatures of keloid. Here we identified immune-related signatures in keloid and explored their pathological mechanisms. Transcriptomic datasets (GSE7890, GSE92566, and GSE44270) of keloid and normal skin tissues were obtained from the Gene Expression Omnibus database. The overlap of differentially expressed genes and immune-related genes was considered as differentially expressed immune-related genes (DEIGs). Functional analysis, expression, and distribution were applied to explore the function and characteristics of DEIGs, and the expression of these DEIGs in keloid and normal skin tissues was verified by immunohistochemistry. Finally, we conducted interactive network analysis and immune infiltration analysis to determine the therapeutic potential and immune correlation. We identified four DEIGs (LGR5, PTN, JAG1, and DKK1). In these datasets, only GSE7890 met the screening criteria. In the GSE7890 dataset, DKK1 and PTN were downregulated in keloid, whereas JAG1 and LGR5 were upregulated in keloid. In addition, we obtained the same conclusion through immunohistochemistry. Functional analysis indicated that these four DEIGs were mainly involved in stem cell, cell cycle, UV response, and therapy resistance. Through interactive network analysis, we found that these DEIGs were associated with drugs currently used to treat keloid, such as hydrocortisone, androstanolone, irinotecan, oxaliplatin, BHQ-880, and lecoleucovorin. Finally, many immune cells, including CD8 T cells, resting memory CD4 T cells, and M1 macrophages, were obtained by immune infiltration analysis. In conclusion, we identified four immune signaling molecules associated with keloid (LGR5, PTN, JAG1, and DKK1). These immune-related signaling molecules may be important modules in the pathogenesis of keloid. Additionally, we developed novel therapeutic targets for the treatment of this challenging disease.
瘢痕疙瘩是一种病因不明的纤维增生性疾病，需要进行不确定的治疗。现有证据表明，免疫系统在瘢痕疙瘩的发生和发展中起着重要作用。然而，对于瘢痕疙瘩的免疫相关特征仍然缺乏研究。在这里，我们鉴定了瘢痕疙瘩中的免疫相关特征，并探讨了它们的病理机制。从基因表达综合数据库中获取了瘢痕疙瘩和正常皮肤组织的转录组数据集（GSE7890、GSE92566 和 GSE44270）。差异表达基因和免疫相关基因的重叠被认为是差异表达的免疫相关基因（DEIGs）。通过功能分析、表达和分布来探索 DEIGs 的功能和特征，并通过免疫组织化学验证这些 DEIGs在瘢痕疙瘩和正常皮肤组织中的表达。最后，我们进行了交互网络分析和免疫浸润分析，以确定治疗潜力和免疫相关性。我们鉴定了四个 DEIGs（LGR5、PTN、JAG1 和 DKK1）。在这些数据集中，只有 GSE7890 符合筛选标准。在 GSE7890 数据集中，DKK1 和 PTN 在瘢痕疙瘩中下调，而 JAG1 和 LGR5 在瘢痕疙瘩中上调。此外，我们通过免疫组织化学也得到了相同的结论。功能分析表明，这四个 DEIGs主要参与了干细胞、细胞周期、UV 反应和治疗抵抗。通过交互网络分析，我们发现这些 DEIGs与目前用于治疗瘢痕疙瘩的药物（如氢化可的松、androstanolone、伊立替康、奥沙利铂、BHQ-880 和亚叶酸钙）有关。最后，通过免疫浸润分析获得了许多免疫细胞，包括 CD8 T 细胞、静止记忆 CD4 T 细胞和 M1 巨噬细胞。总之，我们鉴定了四个与瘢痕疙瘩相关的免疫信号分子（LGR5、PTN、JAG1 和 DKK1）。这些免疫相关信号分子可能是瘢痕疙瘩发病机制中的重要模块。此外，我们为治疗这种具有挑战性的疾病开发了新的治疗靶点。
