Li Wenlin, Wang Yang, Hu Qiang, Li Sainan, Guo Dachuan, Liu Lin, Huang Xiuqing, Dou Lin, Zhou Qi, Shen Tao, Chang Jianmin
Department of Dermatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China.
Int J Med Sci. 2025 Apr 28;22(10):2488-2501. doi: 10.7150/ijms.105650. eCollection 2025.
Basal cell carcinoma (BCC) is the most common type of non-melanoma skin cancer (NMSC). However, few biomarkers have been developed for the diagnosis of BCC. This study aimed to uncover novel BCC biomarkers for diagnosis and treatment via transcriptome and pathogenesis investigations. Microarray datasets of BCC tissues were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified. A total of 558 DEGs were identified between BCC and normal samples from the GSE125285 and GSE42109 datasets. 69 DEGs were expressed in a tissue/organ-specific manner, of which three tissue-specific key genes were finally identified. The three genes showed high performance for BCC diagnosis with AUCs of ≥0.8, indicating that they have high diagnostic significance. CIBERSORT analysis revealed an increase in resting NK cells, M1 macrophages and a decrease in dendritic cells in the immune microenvironment of BCC patients. In addition, versican (VCAN) may be involved in the polarization of M1 macrophages in skin cancer. When VCAN was knocked down, the skin cancer cell line A431 was weakened in terms of proliferation, migration and invasion. Meanwhile, the expression of the key oncogenic factors DDX5 was also reduced and apoptosis was promoted through the BAX/BCL-2/c-Caspase3 pathway. The cell-derived xenograft model study in nude mice showed that knockdown of VCAN in tumour cells significantly suppressed tumour size compared to control tumour cells, suggesting that VCAN is one of the important genes for tumourigenesis. Meanwhile, we examined the level of macrophage M1 polarization in tumour samples from a cell-derived xenograft mouse model, and VCAN knockdown significantly reduced macrophage M1 polarization compared to controls. We also detected the expression of VCAN in tumour samples from BCC patients and verified that VCAN expression was significantly higher in BCC than in normal skin tissue. Thus, VCAN could be a potential clinical target for the diagnosis and treatment of BCC.
基底细胞癌（BCC）是最常见的非黑色素瘤皮肤癌（NMSC）类型。然而，用于诊断BCC的生物标志物却很少。本研究旨在通过转录组和发病机制研究，发现用于诊断和治疗的新型BCC生物标志物。从基因表达综合数据库（GEO）下载BCC组织的微阵列数据集，并鉴定差异表达基因（DEG）。从GSE125285和GSE42109数据集中，共鉴定出BCC与正常样本之间的558个DEG。69个DEG以组织/器官特异性方式表达，最终确定了三个组织特异性关键基因。这三个基因对BCC诊断表现出高性能，曲线下面积（AUC）≥0.8，表明它们具有很高的诊断意义。CIBERSORT分析显示，BCC患者免疫微环境中静息自然杀伤（NK）细胞和M1巨噬细胞增加，树突状细胞减少。此外，多功能蛋白聚糖（VCAN）可能参与皮肤癌中M1巨噬细胞的极化。当敲低VCAN时，皮肤癌细胞系A431在增殖、迁移和侵袭方面均被削弱。同时，关键致癌因子DDX5的表达也降低，并通过BAX/BCL-2/c-半胱天冬酶3途径促进细胞凋亡。裸鼠细胞源异种移植模型研究表明，与对照肿瘤细胞相比，肿瘤细胞中敲低VCAN可显著抑制肿瘤大小，提示VCAN是肿瘤发生的重要基因之一。同时，我们检测了细胞源异种移植小鼠模型肿瘤样本中巨噬细胞M1极化水平，与对照相比，敲低VCAN可显著降低巨噬细胞M1极化。我们还检测了BCC患者肿瘤样本中VCAN的表达，并证实BCC中VCAN表达显著高于正常皮肤组织。因此，VCAN可能是BCC诊断和治疗的潜在临床靶点。
