Transcriptome Analysis Reveals the Molecular Immunological Characteristics of Lesions in Patients with Halo Nevi When Compared to Stable Vitiligo, Normal Nevocytic Nevi and Cutaneous Melanoma

Abstract

Chun Pan,1 Jingzhe Shang,2,3 Haiqin Jiang,1 Ying Shi,1 Wenyue Zhang,1 Jingshu Xiong,1 Youming Mei,1 Siyu Long,1 Gai Ge,1 Zhenzhen Wang,1 Ziwei Wu,1 Hongsheng Wang,1 Aiping Wu2,3 1Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210046, People’s Republic of China; 2Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, People’s Republic of China; 3Suzhou Institute of Systems Medicine, Suzhou, 215123, People’s Republic of ChinaCorrespondence: Hongsheng WangInstitute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210046, People’s Republic of ChinaEmail [email protected] WuInstitute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, People’s Republic of ChinaEmail [email protected]: Given their similar appearance and histology, halo nevi (HN) were considered as a type of vitiligo. However, whether HN have stronger immune response than stable vitiligo (VL) remains unclear. In addition, the molecular alterations in HN compared with normal nevocytic nevi (NN) and primary cutaneous melanoma (MM) must be determined. This study aimed to systematically characterize the molecular immunological features of HN.Methods: Skin samples from patients with HN, VL, NN, and MM were obtained with informed consent. Each of the four groups underwent transcriptome sequencing and data analysis were for pairwise comparison. Quantitative real-time PCR (RT-qPCR) was conducted to confirm the transcriptional expression of some differentially expressed genes (DEGs) that were closely related to immunity.Results: A total of 441 and 1507 DEGs were found in the HN/NN and HN/MM groups, respectively. Compared with those of VL, HN lesions contained 162 up-regulated DEGs and 12 down-regulated DEGs. Bioinformatics analysis showed that the up-regulated genes in HN were substantially enriched in immune response, immune deficiency, and immune rejection; biological stimulation (virus, bacteria); and proliferation and activation of immune cells. Immune cell composition analysis also confirmed high expression levels of multiple immunocytes in HN.Conclusion: The molecular immune mechanisms of HN and VL were similar, but the immune activity of HN was stronger than that of VL. Innate and adaptive immunity were involved in the pathogenesis and progression of HN and VL.Keywords: vitiligo, halo nevi, transcriptome sequencing, differentially expressed genes

Keywords

• vitiligo
• halo nevi
• transcriptome sequencing
• differentially expressed genes