Department of Radiotherapy, Taixing People's Hospital, Taixing, China.
Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Exp Dermatol. 2023 Dec;32(12):2094-2101. doi: 10.1111/exd.14950. Epub 2023 Oct 11.
Basal cell carcinoma (BCC) is the most common malignant tumour arising from the basal cells of the epidermis or follicular structures. The aetiology of BCC is a multifactorial combination of genotype, phenotype and environmental factors. The pathogenesis of BCC remains unclear, with diverse and complex signalling pathways involved. ARHGAP40 is a Rho GTPase-activating protein (RhoGAP). Rho GTPases play a crucial role in the formation and progression of numerous cancers. The expression levels and roles of ARHGAP40 in BCC have not been explored. Here, ARHGAP40 expression was detected in a set of formalin-fixed, paraffin-embedded (FFPE) samples of basal cell carcinoma, paracancerous normal skin and benign skin lesions. The epigenetic mechanism that downregulates ARHGAP40 in basal cell carcinoma was investigated. We found that ARHGAP40 is expressed in normal basal cells and most benign skin lesions but lost in most basal cell carcinomas. We detected CpG island hypermethylation at the promoter-associated region of ARHGAP40. Our data suggest that ARHGAP40 is downregulated in BCC due to hypermethylation. ARHGAP40 protein is a potential novel biomarker for distinguishing trichoblastoma from BCC. This report is preliminary, and extensive research into the role of ARHGAP40 in BCC carcinogenesis and its potential as a treatment target is required in the future.
基底细胞癌（BCC）是最常见的来源于表皮基底细胞或毛囊结构的恶性肿瘤。BCC 的病因是基因型、表型和环境因素的多因素组合。BCC 的发病机制尚不清楚，涉及多种复杂的信号通路。ARHGAP40 是一种 Rho GTPase 激活蛋白（RhoGAP）。Rho GTPases 在多种癌症的形成和进展中起着至关重要的作用。ARHGAP40 在 BCC 中的表达水平和作用尚未得到探索。在这里，我们在一组福尔马林固定、石蜡包埋（FFPE）的基底细胞癌、癌旁正常皮肤和良性皮肤病变样本中检测了 ARHGAP40 的表达。研究了下调基底细胞癌中 ARHGAP40 的表观遗传机制。我们发现 ARHGAP40 在正常基底细胞和大多数良性皮肤病变中表达，但在大多数基底细胞癌中丢失。我们在 ARHGAP40 启动子相关区域检测到 CpG 岛超甲基化。我们的数据表明，由于 hypermethylation，ARHGAP40 在 BCC 中下调。ARHGAP40 蛋白是区分毛母细胞瘤和 BCC 的潜在新型生物标志物。本报告只是初步的，未来还需要进一步研究 ARHGAP40 在 BCC 癌变中的作用及其作为治疗靶点的潜力。
