Sha Yan, Mao An-Qi, Liu Yuan-Jie, Li Jie-Pin, Gong Ya-Ting, Xiao Dong, Huang Jun, Gao Yan-Wei, Wu Mu-Yao, Shen Hui
Departments of Dermatology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, People's Republic of China.
Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People's Republic of China.
Pharmgenomics Pers Med. 2023 Mar 4;16:153-172. doi: 10.2147/PGPM.S399886. eCollection 2023.
The incidence of cutaneous melanoma continues to rise rapidly and has an extremely poor prognosis. Immunotherapy strategies are the most effective approach for patients who have developed metastases, but not all cases have been successful due to the complex and variable mechanisms of melanoma response to immune checkpoint inhibition.
We synthesized collagen-coding gene expression data (second-generation and single-cell sequencing) from public Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Bioinformatics analysis was performed using R software and several database resources such as Metascape database, Gene Set Cancer Analysis (GSCA) database, and Cytoscape software, etc., to investigate the biological mechanisms that may be related with collagens. Immunofluorescence and immunohistochemical staining were used to validate the expression and localization of Nidogen-2 (NID2).
Melanoma patients can be divided into two collagen clusters. Patients with high collagen levels (C1) had a shorter survival than those with low collagen levels (C2) and were less likely to benefit from immunotherapy. We demonstrated that NID2 is a potential key factor in the collagen phenotype, is involved in fibroblast activation in melanoma, and forms a barrier to limit the proximity of CD8+ T cells to tumor cells.
We clarified the adverse effects of collagen on melanoma patients and identified NID2 as a potential therapeutic target.
皮肤黑色素瘤的发病率持续快速上升，预后极差。免疫治疗策略是已发生转移患者最有效的治疗方法，但由于黑色素瘤对免疫检查点抑制反应的机制复杂且多变，并非所有病例都取得成功。
我们从公共基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库中合成了胶原蛋白编码基因表达数据（二代测序和单细胞测序）。使用R软件以及诸如Metascape数据库、基因集癌症分析（GSCA）数据库和Cytoscape软件等多个数据库资源进行生物信息学分析，以研究可能与胶原蛋白相关的生物学机制。采用免疫荧光和免疫组织化学染色来验证巢蛋白-2（NID2）的表达和定位。
黑色素瘤患者可分为两个胶原蛋白簇。胶原蛋白水平高的患者（C1）比胶原蛋白水平低的患者（C2）生存期更短，且从免疫治疗中获益的可能性更小。我们证明NID2是胶原蛋白表型中的一个潜在关键因子，参与黑色素瘤中的成纤维细胞活化，并形成一道屏障限制CD8+T细胞与肿瘤细胞的接近。
我们阐明了胶原蛋白对黑色素瘤患者的不利影响，并确定NID2为一个潜在的治疗靶点。
